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Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03330405
Recruitment Status : Terminated (The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the investigational treatments have been moved to a continuation study (NCT05059522).)
First Posted : November 6, 2017
Results First Posted : June 12, 2023
Last Update Posted : October 13, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Primary or Recurrent) or Metastatic Solid Tumors
Interventions Drug: Avelumab Phase 1b
Drug: Talazoparib Phase 1b
Drug: Avelumab Phase 2
Drug: Talazoparib Phase 2
Enrollment 223
Recruitment Details The study was conducted in 2 phases: Phase 1b (talazoparib dose level cohorts) and Phase 2 (expansion phase). The Phase 1b study design started at the highest dose of talazoparib (1 mg QD), to be de-escalated to 0.75 and 0.5 mg QD. With DLT rate <33% among 12 DLT-evaluable patients treated at 1 mg, Phase 2 started. The 2 cohorts at lower dose did not enroll any participants and are not displayed in the results. Only the Phase 1b cohort "Avelumab 800 mg Q2W + Talazoparib 1 mg QD" is displayed.
Pre-assignment Details Phase 1b: 12 participants were enrolled and assigned to study treatment. Phase 2: 211 participants were enrolled and assigned to study treatment.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally once daily (QD) in combination with avelumab 800 mg intravenously (IV) every 2 weeks (Q2W) for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Period Title: Overall Study
Started 12 42 5 22 23 20 11 40 21 18 9
Completed 0 0 0 0 0 0 0 0 0 0 0
Not Completed 12 42 5 22 23 20 11 40 21 18 9
Reason Not Completed
Other             1             3             1             0             2             0             1             0             0             0             0
Progressive disease             8             27             4             18             16             14             7             29             9             11             5
Withdrawal by Subject             1             4             0             1             1             1             0             2             2             1             1
Global deterioration of health status             2             3             0             2             3             3             0             2             8             4             1
Adverse Event             0             1             0             1             1             1             3             4             2             2             2
Death             0             4             0             0             0             1             0             2             0             0             0
Physician Decision             0             0             0             0             0             0             0             1             0             0             0
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated) Total
Hide Arm/Group Description Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally once daily (QD) in combination with avelumab 800 mg intravenously (IV) every 2 weeks (Q2W) for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Total of all reporting groups
Overall Number of Baseline Participants 12 42 5 22 23 20 11 40 21 18 9 223
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Mean Number Analyzed 12 participants 42 participants 5 participants 22 participants 23 participants 20 participants 11 participants 40 participants 21 participants 18 participants 9 participants 223 participants
62.67  (9.49) 67.00  (9.37) 59.60  (7.40) 56.18  (12.49) 53.83  (14.08) 62.65  (10.66) 61.36  (9.24) 65.73  (9.19) 63.71  (7.40) 71.56  (7.37) 63.00  (10.91) 63.17  (11.04)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 12 participants 42 participants 5 participants 22 participants 23 participants 20 participants 11 participants 40 participants 21 participants 18 participants 9 participants 223 participants
<65 years
6
  50.0%
15
  35.7%
4
  80.0%
15
  68.2%
17
  73.9%
12
  60.0%
7
  63.6%
16
  40.0%
8
  38.1%
3
  16.7%
5
  55.6%
108
  48.4%
65 - <75 years
5
  41.7%
19
  45.2%
1
  20.0%
6
  27.3%
3
  13.0%
5
  25.0%
3
  27.3%
16
  40.0%
12
  57.1%
8
  44.4%
2
  22.2%
80
  35.9%
75 - <85 years
1
   8.3%
7
  16.7%
0
   0.0%
1
   4.5%
3
  13.0%
3
  15.0%
1
   9.1%
7
  17.5%
1
   4.8%
6
  33.3%
2
  22.2%
32
  14.3%
>= 85 years
0
   0.0%
1
   2.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.5%
0
   0.0%
1
   5.6%
0
   0.0%
3
   1.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 42 participants 5 participants 22 participants 23 participants 20 participants 11 participants 40 participants 21 participants 18 participants 9 participants 223 participants
Female
3
  25.0%
9
  21.4%
2
  40.0%
22
 100.0%
22
  95.7%
20
 100.0%
11
 100.0%
14
  35.0%
0
   0.0%
0
   0.0%
3
  33.3%
106
  47.5%
Male
9
  75.0%
33
  78.6%
3
  60.0%
0
   0.0%
1
   4.3%
0
   0.0%
0
   0.0%
26
  65.0%
21
 100.0%
18
 100.0%
6
  66.7%
117
  52.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 42 participants 5 participants 22 participants 23 participants 20 participants 11 participants 40 participants 21 participants 18 participants 9 participants 223 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.3%
0
   0.0%
0
   0.0%
2
   5.0%
3
  14.3%
1
   5.6%
0
   0.0%
7
   3.1%
Not Hispanic or Latino
12
 100.0%
39
  92.9%
5
 100.0%
19
  86.4%
21
  91.3%
18
  90.0%
11
 100.0%
38
  95.0%
11
  52.4%
16
  88.9%
8
  88.9%
198
  88.8%
Unknown or Not Reported
0
   0.0%
3
   7.1%
0
   0.0%
3
  13.6%
1
   4.3%
2
  10.0%
0
   0.0%
0
   0.0%
7
  33.3%
1
   5.6%
1
  11.1%
18
   8.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 12 participants 42 participants 5 participants 22 participants 23 participants 20 participants 11 participants 40 participants 21 participants 18 participants 9 participants 223 participants
Black or African American
3
  25.0%
1
   2.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  18.2%
1
   2.5%
5
  23.8%
2
  11.1%
0
   0.0%
14
   6.3%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.4%
Asian
0
   0.0%
5
  11.9%
0
   0.0%
1
   4.5%
1
   4.3%
0
   0.0%
3
  27.3%
2
   5.0%
1
   4.8%
2
  11.1%
0
   0.0%
15
   6.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.4%
White
9
  75.0%
34
  81.0%
4
  80.0%
20
  90.9%
17
  73.9%
18
  90.0%
6
  54.5%
36
  90.0%
12
  57.1%
14
  77.8%
9
 100.0%
179
  80.3%
Not reported
0
   0.0%
2
   4.8%
0
   0.0%
1
   4.5%
4
  17.4%
2
  10.0%
0
   0.0%
1
   2.5%
3
  14.3%
0
   0.0%
0
   0.0%
13
   5.8%
Geographic Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 42 participants 5 participants 22 participants 23 participants 20 participants 11 participants 40 participants 21 participants 18 participants 9 participants 223 participants
North America
12
 100.0%
9
  21.4%
3
  60.0%
14
  63.6%
15
  65.2%
10
  50.0%
7
  63.6%
15
  37.5%
20
  95.2%
11
  61.1%
8
  88.9%
124
  55.6%
Western Europe
0
   0.0%
10
  23.8%
2
  40.0%
0
   0.0%
1
   4.3%
2
  10.0%
1
   9.1%
5
  12.5%
1
   4.8%
4
  22.2%
1
  11.1%
27
  12.1%
Eastern Europe
0
   0.0%
19
  45.2%
0
   0.0%
6
  27.3%
4
  17.4%
5
  25.0%
1
   9.1%
16
  40.0%
0
   0.0%
1
   5.6%
0
   0.0%
52
  23.3%
Australasia
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.1%
2
   8.7%
3
  15.0%
0
   0.0%
2
   5.0%
0
   0.0%
1
   5.6%
0
   0.0%
10
   4.5%
Asia
0
   0.0%
4
   9.5%
0
   0.0%
0
   0.0%
1
   4.3%
0
   0.0%
2
  18.2%
2
   5.0%
0
   0.0%
1
   5.6%
0
   0.0%
10
   4.5%
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 42 participants 5 participants 22 participants 23 participants 20 participants 11 participants 40 participants 21 participants 18 participants 9 participants 223 participants
0
4
  33.3%
5
  11.9%
1
  20.0%
12
  54.5%
12
  52.2%
9
  45.0%
8
  72.7%
16
  40.0%
4
  19.0%
6
  33.3%
1
  11.1%
78
  35.0%
1
8
  66.7%
37
  88.1%
4
  80.0%
10
  45.5%
11
  47.8%
11
  55.0%
3
  27.3%
24
  60.0%
17
  81.0%
12
  66.7%
8
  88.9%
145
  65.0%
[1]
Measure Description: ECOG=Eastern Cooperative Oncology Group. Score 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work or office work.
1.Primary Outcome
Title Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
Hide Description DLTs=occurrence of any of the following AEs attributable to any study treatment in Cycle 1:Hematologic: grade(G)4 neutropenia lasting >5 days (absolute neutrophil count [ANC]< 0.5*10^9/L); febrile neutropenia; neutropenic infection (ANC<1.0*10^9/L, and G>3 infection); G>=3 thrombocytopenia (platelet count [PC] <50.0*10^9/L) with bleeding; G4 thrombocytopenia (PC<25.0*10^9/L); G4 anemia (life-threatening; urgent intervention indicated). Non-hematologic: G>=3 toxicities unless predefined in the protocol; potential Hy's law cases. Non-adherence to treatment schedule: failure to deliver at least 75% of the planned doses of talazoparib during the first cycle of treatment due to treatment-related toxicities; G3 non-hematologic toxicity that delayed administration of either study drug for more than 2 weeks. Dose reductions: any adverse event (AE) that resulted in a dose reduction of talazoparib.
Time Frame Cycle 1; 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The DLT analysis set was a subset of the safety analysis set and included all enrolled participants in the Phase 1b portion who were eligible for the study, received at least 1 dose of the combination treatment, and either experienced DLT during the first cycle (28 days) of treatment, or completed the DLT observation period for the first cycle of treatment.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
3
  25.0%
2.Primary Outcome
Title Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
Hide Description This outcome measure (OM) is reported for participants with solid tumors except mCRPC; for those participants, OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version(v) 1.1 by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis <10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-progressive disease (PD), where PD is unequivocal progression of pre-existing lesions.
Time Frame From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)
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Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was not planned to be collected and analyzed for Phase 1b arm. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 42 5 22 23 20 11 40 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
16.7
(7.0 to 31.4)
20.0
(0.5 to 71.6)
18.2
(5.2 to 40.3)
34.8
(16.4 to 57.3)
20.0
(5.7 to 43.7)
63.6
(30.8 to 89.1)
15.0
(5.7 to 29.8)
0
(0.0 to 41.0)
3.Primary Outcome
Title Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment
Hide Description This OM is reported for participants with mCRPC; for those participants, OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per PCWG3 criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis <10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.
Time Frame From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was not planned to be collected and analyzed for Phase 1b arm. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
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Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 21 18 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
0
(0.0 to 16.1)
11.1
(1.4 to 34.7)
50.0
(1.3 to 98.7)
4.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description Adverse event (AE) was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with all-causality TEAEs
12
 100.0%
207
  98.1%
Participants with treatment-related TEAEs
11
  91.7%
197
  93.4%
5.Secondary Outcome
Title Number of Participants With Grade >=3 TEAEs
Hide Description AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with Grade 3 or higher TEAEs were reported.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with all-causality Grade >=3 TEAEs
9
  75.0%
156
  73.9%
Participants with treatment-related Grade >=3 TEAEs
9
  75.0%
120
  56.9%
6.Secondary Outcome
Title Number of Participants With Serious TEAEs
Hide Description TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs). A serious TEAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/considered to be an important medical event: death; life-threatening experience (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with all-causality serious TEAEs
1
   8.3%
75
  35.5%
Participants with treatment-related serious TEAEs
1
   8.3%
25
  11.8%
7.Secondary Outcome
Title Number of Participants With TEAEs Leading to Discontinuation of Either Study Drug
Hide Description Either study drug = avelumab only or talazoparib only. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with all-causality TEAEs leading to discontinuation of avelumab only
0
   0.0%
5
   2.4%
Participants with treatment-related TEAEs leading to discontinuation of avelumab only
0
   0.0%
4
   1.9%
Participants with all-causality TEAEs leading to discontinuation of talazoparib only
1
   8.3%
9
   4.3%
Participants with treatment-related TEAEs leading to discontinuation of talazoparib only
1
   8.3%
8
   3.8%
8.Secondary Outcome
Title Number of Participants With TEAEs Leading to Discontinuation of All Study Drugs
Hide Description All study drugs = all study drugs in the combination. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with all-causality TEAEs leading to discontinuation of all study drugs
1
   8.3%
20
   9.5%
Participants with treatment-related TEAEs leading to discontinuation of all study drugs
0
   0.0%
1
   0.5%
9.Secondary Outcome
Title Number of Participants With TEAEs Leading to Death
Hide Description TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with all-causality TEAEs leading to death
0
   0.0%
21
  10.0%
Participants with treatment-related TEAEs leading to death
0
   0.0%
1
   0.5%
10.Secondary Outcome
Title Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period
Hide Description The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan. Here 'number analyzed' signifies participants evaluable for specified rows.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Activated partial thromboplastin time prolonged Number Analyzed 11 participants 143 participants
4
  36.4%
21
  14.7%
Anemia Number Analyzed 12 participants 208 participants
8
  66.7%
161
  77.4%
Hemoglobin increased Number Analyzed 12 participants 208 participants
0
   0.0%
1
   0.5%
Lymphocyte count decreased Number Analyzed 12 participants 208 participants
9
  75.0%
145
  69.7%
Lymphocyte count increased Number Analyzed 12 participants 208 participants
1
   8.3%
3
   1.4%
Neutrophil count decreased Number Analyzed 12 participants 208 participants
8
  66.7%
100
  48.1%
Platelet count decreased Number Analyzed 12 participants 208 participants
6
  50.0%
141
  67.8%
White blood cell decreased Number Analyzed 12 participants 208 participants
10
  83.3%
139
  66.8%
11.Secondary Outcome
Title Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period
Hide Description The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan. Here 'number analyzed' signifies participants evaluable for specified rows.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Activated partial thromboplastin time prolonged Number Analyzed 11 participants 143 participants
0
   0.0%
1
   0.7%
Anemia Number Analyzed 12 participants 208 participants
4
  33.3%
78
  37.5%
Lymphocyte count decreased Number Analyzed 12 participants 208 participants
4
  33.3%
44
  21.2%
Neutrophil count decreased Number Analyzed 12 participants 208 participants
5
  41.7%
27
  13.0%
Platelet count decreased Number Analyzed 12 participants 208 participants
4
  33.3%
47
  22.6%
White blood cell decreased Number Analyzed 12 participants 208 participants
3
  25.0%
20
   9.6%
12.Secondary Outcome
Title Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period
Hide Description The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan. Here 'number analyzed' signifies participants evaluable for specified rows.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase increased Number Analyzed 12 participants 208 participants
1
   8.3%
41
  19.7%
Alkaline phosphatase increased Number Analyzed 12 participants 208 participants
3
  25.0%
74
  35.6%
Aspartate aminotransferase increased Number Analyzed 12 participants 208 participants
2
  16.7%
53
  25.5%
Blood bilirubin increased Number Analyzed 12 participants 208 participants
0
   0.0%
24
  11.5%
Creatinine Phosphokinase (CPK) increased Number Analyzed 12 participants 206 participants
2
  16.7%
37
  18.0%
Creatinine increased Number Analyzed 12 participants 208 participants
9
  75.0%
147
  70.7%
Gamma-glutamyl transferase (GGT) increased Number Analyzed 12 participants 206 participants
2
  16.7%
69
  33.5%
Hypercalcemia Number Analyzed 12 participants 208 participants
1
   8.3%
23
  11.1%
Hyperglycemia Number Analyzed 12 participants 208 participants
0
   0.0%
48
  23.1%
Hyperkalemia Number Analyzed 12 participants 208 participants
2
  16.7%
25
  12.0%
Hypermagnesemia Number Analyzed 12 participants 207 participants
0
   0.0%
21
  10.1%
Hypernatremia Number Analyzed 12 participants 208 participants
0
   0.0%
9
   4.3%
Hypoalbuminemia Number Analyzed 12 participants 208 participants
2
  16.7%
60
  28.8%
Hypocalcemia Number Analyzed 12 participants 208 participants
1
   8.3%
45
  21.6%
Hypoglycemia Number Analyzed 12 participants 208 participants
0
   0.0%
13
   6.3%
Hypokalemia Number Analyzed 12 participants 208 participants
3
  25.0%
36
  17.3%
Hypomagnesemia Number Analyzed 12 participants 207 participants
2
  16.7%
33
  15.9%
Hyponatremia Number Analyzed 12 participants 208 participants
4
  33.3%
66
  31.7%
Hypophosphatemia Number Analyzed 12 participants 206 participants
2
  16.7%
43
  20.9%
Lipase increased Number Analyzed 12 participants 207 participants
4
  33.3%
36
  17.4%
Serum amylase increased Number Analyzed 12 participants 207 participants
2
  16.7%
32
  15.5%
13.Secondary Outcome
Title Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period
Hide Description The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan. Here 'number analyzed' signifies participants evaluable for specified rows.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase increased Number Analyzed 12 participants 208 participants
0
   0.0%
2
   1.0%
Alkaline phosphatase increased Number Analyzed 12 participants 208 participants
0
   0.0%
7
   3.4%
Aspartate aminotransferase increased Number Analyzed 12 participants 208 participants
0
   0.0%
2
   1.0%
Blood bilirubin increased Number Analyzed 12 participants 208 participants
0
   0.0%
3
   1.4%
Creatinine Phosphokinase (CPK) increased Number Analyzed 12 participants 206 participants
0
   0.0%
4
   1.9%
Creatinine increased Number Analyzed 12 participants 208 participants
0
   0.0%
2
   1.0%
Gamma-glutamyl transferase (GGT) increased Number Analyzed 12 participants 206 participants
0
   0.0%
11
   5.3%
Hyperglycemia Number Analyzed 12 participants 208 participants
0
   0.0%
6
   2.9%
Hyperkalemia Number Analyzed 12 participants 208 participants
0
   0.0%
1
   0.5%
Hypermagnesemia Number Analyzed 12 participants 207 participants
0
   0.0%
5
   2.4%
Hypoalbuminemia Number Analyzed 12 participants 208 participants
0
   0.0%
2
   1.0%
Hypocalcemia Number Analyzed 12 participants 208 participants
0
   0.0%
4
   1.9%
Hypokalemia Number Analyzed 12 participants 208 participants
0
   0.0%
1
   0.5%
Hyponatremia Number Analyzed 12 participants 208 participants
0
   0.0%
12
   5.8%
Hypophosphatemia Number Analyzed 12 participants 206 participants
1
   8.3%
6
   2.9%
Lipase increased Number Analyzed 12 participants 207 participants
0
   0.0%
14
   6.8%
Serum amylase increased Number Analyzed 12 participants 207 participants
0
   0.0%
7
   3.4%
14.Secondary Outcome
Title Trough Concentrations (Ctrough)/Predose and Maximum Concentrations (Cmax) of Serum Avelumab Concentrations (μg/mL) by Visit (Excluding Site 1055)
Hide Description Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle.
Time Frame Predose/0 Hour (H) and 1 H on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4, and additionally on Day 1 of Cycles 6, 9, 12, 18, and 24.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK concentration analysis sets (1 unique set for each study drug used in the combination) were subsets of safety analysis set including participants with >=1 post-dose concentration measurement above the lower limit of quantitation (LLQ) for avelumab/talazoparib. Cohorts were combined as pre-specified in reporting and analysis plan. Site 1055 was excluded as samples were not meeting the protocol requirements. Here 'number analyzed' signifies participants evaluable for specified rows.
Arm/Group Title Phase 1b and Phase 2 Combined
Hide Arm/Group Description:
Treatment = Avelumab 800 mg IV Infusion Q2W coadministered with Talazoparib 1 mg QD.
Overall Number of Participants Analyzed 194
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
Cycle 1 / Day 1 (0 Hour [H]) Number Analyzed 194 participants
NA [1] 
(NA%)
Cycle 1 / Day 1 (1 H) Number Analyzed 178 participants
221.0
(41%)
Cycle 1 / Day 15 (0 H) Number Analyzed 183 participants
21.20
(72%)
Cycle 1 / Day 15 (1 H) Number Analyzed 164 participants
206.6
(86%)
Cycle 2 / Day 1 (0 H) Number Analyzed 168 participants
26.41
(68%)
Cycle 2 / Day 1 (1 H) Number Analyzed 156 participants
199.6
(110%)
Cycle 3 / Day 1 (0 H) Number Analyzed 120 participants
31.45
(80%)
Cycle 3 / Day 1 (1 H) Number Analyzed 126 participants
188.8
(105%)
Cycle 4 / Day 1 (0 H) Number Analyzed 106 participants
34.59
(81%)
Cycle 4 / Day 1 (1 H) Number Analyzed 114 participants
190.6
(99%)
Cycle 6 / Day 1 (0 H) Number Analyzed 78 participants
37.40
(73%)
Cycle 6 / Day 1 (1 H) Number Analyzed 81 participants
185.9
(98%)
Cycle 9 / Day 1 (0 H) Number Analyzed 40 participants
39.97
(91%)
Cycle 9 / Day 1 (1 H) Number Analyzed 44 participants
171.1
(145%)
Cycle 12 / Day 1 (0 H) Number Analyzed 18 participants
47.10
(63%)
Cycle 12 / Day 1 (1 H) Number Analyzed 18 participants
202.9
(88%)
Cycle 18 / Day 1 (0 H) Number Analyzed 3 participants
53.94
(33%)
Cycle 18 / Day 1 (1 H) Number Analyzed 3 participants
135.6
(354%)
Cycle 24 / Day 1 (0 H) Number Analyzed 1 participants
76.40 [2] 
(NA%)
Cycle 24 / Day 1 (1 H) Number Analyzed 1 participants
378.0 [2] 
(NA%)
[1]
The result was Not Available as no observations were above the avelumab LLQ of 0.2 μg/mL.
[2]
Only 1 participant evaluable for this timepoint. Coefficient of variation is not applicable.
15.Secondary Outcome
Title Predose and Postdose Plasma Talazoparib Concentrations (pg/mL) by Visit (Excluding Site 1055)
Hide Description Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle. Cmax=maximum concentration. Ctrough=trough concentration. Participants with moderate renal impairment were started at a lower, 0.75 mg QD, dose to compensate for decreased talazoparib clearance.
Time Frame Pre-dose and post-dose (at the end of the avelumab infusion) on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK concentration analysis sets (1 unique set for each study drug used in the combination) were subsets of safety analysis set including participants with >=1 post-dose concentration measurement above the lower limit of quantitation (LLQ) for avelumab/talazoparib. Cohorts were combined as pre-specified in reporting and analysis plan. Site 1055 was excluded as samples were not meeting the protocol requirements. Here 'number analyzed' signifies participants evaluable for specified rows.
Arm/Group Title Talazoparib Starting Dose = 1 mg QD Talazoparib Starting Dose = 0.75 mg QD
Hide Arm/Group Description:
Treatment = Avelumab 800 mg IV Infusion Q2W coadministered with Talazoparib 1 mg QD (participants with normal renal function or mild renal impairment).
Treatment = Avelumab 800 mg IV Infusion Q2W coadministered with Talazoparib 0.75 mg QD (participants with moderate renal impairment)
Overall Number of Participants Analyzed 163 31
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: pg/mL
Cycle 1 / Day 1 (Predose) Number Analyzed 163 participants 31 participants
NA [1] 
(NA%)
NA [1] 
(NA%)
Cycle 1 / Day 1 (Postdose) Number Analyzed 46 participants 12 participants
2295
(137%)
2015
(112%)
Cycle 1 / Day 15 (Predose) Number Analyzed 72 participants 10 participants
4672
(63%)
4657
(47%)
Cycle 1 / Day 15 (Postdose) Number Analyzed 33 participants 3 participants
9055
(88%)
8257
(11%)
Cycle 2 / Day 1 (Predose) Number Analyzed 66 participants 10 participants
4385
(53%)
5871
(53%)
Cycle 2 / Day 1 (Postdose) Number Analyzed 21 participants 5 participants
8479
(73%)
9834
(62%)
Cycle 3 / Day 1 (Predose) Number Analyzed 47 participants 6 participants
4212
(46%)
3874
(48%)
Cycle 3 / Day 1 (Postdose) Number Analyzed 22 participants 3 participants
6765
(239%)
1236
(8074%)
Cycle 4 / Day 1 (Predose) Number Analyzed 29 participants 6 participants
4713
(38%)
3826
(73%)
Cycle 4 / Day 1 (Postdose) Number Analyzed 15 participants 3 participants
6506
(76%)
6735
(70%)
[1]
The result was Not Available as no observations were above the talazoparib LLQ of 25 pg/mL.
16.Secondary Outcome
Title Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)
Hide Description Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively.
Time Frame Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycle 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis set was a subset of the safety analysis set and included participants who had at least 1 ADA/Nab sample collected for avelumab. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
N0
12
 100.0%
211
 100.0%
N1
12
 100.0%
209
  99.1%
N2
11
  91.7%
202
  95.7%
N3
11
  91.7%
200
  94.8%
17.Secondary Outcome
Title Number of Participants by ADA Categories
Hide Description Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA Result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively. n=number of participants in each category.
Time Frame Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycles 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis set was a subset of the safety analysis set and included participants who had at least 1 ADA/Nab sample collected for avelumab. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All participants from Cohort A to Cohort F combined.
Overall Number of Participants Analyzed 12 211
Measure Type: Count of Participants
Unit of Measure: Participants
ADA never-positive (n/N0)
12
 100.0%
205
  97.2%
ADA ever-positive (n/N0)
0
   0.0%
6
   2.8%
ADA ever-positive: Baseline ADA positive (n/N1) (No treatment-boosted ADA [n/N2])
0
   0.0%
4
   1.9%
ADA ever-positive: Treatment-induced ADA positive (n/N3)
0
   0.0%
2
   0.9%
18.Secondary Outcome
Title Phase 1b: Percentage of Participants With Confirmed OR as Per RECIST v1.1 and PCWG3 by Investigator Assessment
Hide Description This OM is reported for participants in Phase 1b; OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis <10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.
Time Frame From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 1b arm only.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Particpants
16.7
(2.1 to 48.4)
19.Secondary Outcome
Title Phase 1b: Time to Response (TTR) in Participants With Confirmed CR or PR
Hide Description For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
Time Frame From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<=5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 1b arm only. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 2
Median (Full Range)
Unit of Measure: Months
1.8
(1.8 to 1.8)
20.Secondary Outcome
Title Phase 2: TTR in Participants With Confirmed CR or PR
Hide Description For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
Time Frame From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<= 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 2 only. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 7 1 4 8 4 7 6 2 1
Median (Full Range)
Unit of Measure: Months
3.7
(1.7 to 11.3)
1.8
(1.8 to 1.8)
1.8
(1.6 to 2.0)
1.9
(1.6 to 3.6)
3.6
(1.7 to 17.9)
1.7
(1.6 to 3.7)
2.1
(1.4 to 5.9)
5.5
(5.4 to 5.6)
1.8
(1.8 to 1.8)
21.Secondary Outcome
Title Phase 2: Duration of Response (DR) in Participants With Confirmed CR or PR
Hide Description For participants with solid tumors except mCRPC, DR was defined for participants with confirmed OR (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.
Time Frame From the first objective tumor response/soft tissue response to the first objective tumor progression/subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first (<=5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 2 only. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure; Cohorts without evaluable participants for this outcome measure [i.e., Phase 2: Cohort E1 (mCRPC), Phase 2: Cohort E2 (mCRPC DDR+), Phase 2: Cohort F (BRCA/ATM-mutated)] are not presented.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 7 1 4 8 4 7 6
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% CI were not estimated for <10 participants
22.Secondary Outcome
Title Phase 1b: Progression-Free Survival (PFS) in Participants With Confirmed CR or PR
Hide Description For participants with solid tumors except mCRPC, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first
Time Frame From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 1b only.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally QD in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: Months
6.0
(1.8 to 11.5)
23.Secondary Outcome
Title Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1)
Hide Description This OM is reported for participants with solid tumors except mCRPC; for those participants, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first.
Time Frame From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 2 only. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 42 5 22 23 20 11 40 7
Median (95% Confidence Interval)
Unit of Measure: Months
4.7
(3.7 to 7.4)
1.9 [1] 
(1.8 to NA)
3.6
(1.9 to 5.6)
5.3
(2.0 to 12.8)
7.2
(4.0 to 9.1)
16.8 [1] 
(7.2 to NA)
3.6
(1.9 to 5.4)
1.7
(1.4 to 3.3)
[1]
Upper limit of 95% CI was not reached due to fewer number of participants with event.
24.Secondary Outcome
Title Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1 and PCWG3)
Hide Description This OM was reported for participants with mCRPC; for these participants, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first.
Time Frame From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 2 only. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 21 18 2
Median (95% Confidence Interval)
Unit of Measure: Months
4.1 [1] 
(1.9 to NA)
4.6
(1.7 to 9.8)
8.4
(5.9 to 10.9)
[1]
Upper limit of 95% CI was not reached due to fewer number of participants with event.
25.Secondary Outcome
Title Phase 2: Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC
Hide Description Time to PSA progression for participants with mCRPC was defined as the time from the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained >=3 weeks (21 days) later.
Time Frame From the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Phase 2 only. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 21 18 2
Median (95% Confidence Interval)
Unit of Measure: Months
1.0
(1.0 to 4.6)
2.8
(1.0 to 6.5)
3.1
(1.6 to 4.6)
26.Secondary Outcome
Title Phase 1b: Overall Survival
Hide Description Overall survival (OS) was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
Time Frame From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was for Phase 1b only.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: Months
18.5 [1] 
(6.4 to NA)
[1]
Upper limit of 95% CI was not reached due to fewer number of participants with event.
27.Secondary Outcome
Title Phase 2: Overall Survival
Hide Description OS was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
Time Frame From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was for Phase 2 only.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 42 5 22 23 20 11 40 21 18 9
Median (95% Confidence Interval)
Unit of Measure: Months
11.6
(8.4 to 14.9)
26.3
(3.5 to 43.3)
8.2
(5.8 to 13.0)
27.5
(12.6 to 40.2)
22.9 [1] 
(7.8 to NA)
38.8 [1] 
(16.9 to NA)
13.1
(8.5 to 19.2)
15.9
(9.6 to 20.7)
16.1
(10.8 to 23.4)
6.9
(1.4 to 27.4)
[1]
Upper limit of 95% CI was not reached due to fewer number of participants with event.
28.Secondary Outcome
Title Phase 2: Percentage of Participants With PSA Response
Hide Description PSA response was defined as the proportion of participants with confirmed PSA decline >=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must be confirmed by a second consecutive value at least 3 weeks later.
Time Frame From baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50% (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was planned for Cohorts E1, E2, and F in Phase 2 only as pre-specified in reporting and analysis plan. Cohorts without evaluable participants for this outcome measure [ie, Phase 2: Cohort F (BRCA/ATM-mutated)] are not presented.
Arm/Group Title Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+)
Hide Arm/Group Description:
Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 21 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
9.5
(1.2 to 30.4)
5.6
(0.1 to 27.3)
29.Secondary Outcome
Title Phase 1b: Percentage of Participants With CA-125 Response
Hide Description Cancer Antigen 125 (CA-125) response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
Time Frame From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was for Phase 1b only. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD
Hide Arm/Group Description:
Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
100
(2.5 to 100.0)
30.Secondary Outcome
Title Phase 2: Percentage of Participants With CA-125 Response
Hide Description CA-125 response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
Time Frame From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was for Cohorts C1 and C2 in Phase 2 only as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 20 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
45.0
(23.1 to 68.5)
63.6
(30.8 to 89.1)
31.Secondary Outcome
Title Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline
Hide Description PD-L1 expression on tumor and infiltrating immune cells were measured by immunohistochemistry (IHC). PD-L1 expression level corresponds to the percentage of positive cells. The PD-L1 Positive category does not apply to cohorts A1 and A2. The PD-L1 High/Low categories only apply to cohorts A1 and A2. Participants were considered positive if their baseline tumor tissue sample demonstrated cell surface PD-L1 expression: 1) for Cohorts E1, E2, and F: >=1% tumor cells (TC) or >= 5% immune cells (IC); 2) for Cohort D: TC/IC>=25%; 3) for Cohorts B1, B2, C1, C2: IC>=5%; otherwise were considered negative. Categories based on PD-L1 expression level ≥50% and <50% were defined as High and Low, respectively.
Time Frame At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this outcome measure was presented for Phase 2 only as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 42 5 22 23 20 11 40 21 18 9
Measure Type: Count of Participants
Unit of Measure: Participants
High
3
   7.1%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Low
8
  19.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Positive (Not applicable for Cohorts A1 and A2)
0
   0.0%
0
   0.0%
8
  36.4%
3
  13.0%
5
  25.0%
5
  45.5%
13
  32.5%
1
   4.8%
2
  11.1%
0
   0.0%
Negative
22
  52.4%
2
  40.0%
6
  27.3%
16
  69.6%
13
  65.0%
4
  36.4%
19
  47.5%
13
  61.9%
12
  66.7%
3
  33.3%
Unknown
9
  21.4%
1
  20.0%
8
  36.4%
4
  17.4%
2
  10.0%
2
  18.2%
8
  20.0%
7
  33.3%
4
  22.2%
6
  66.7%
32.Secondary Outcome
Title Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline
Hide Description TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. High: TMB score >=20 muts/mb (number of mutations per megabase of DNA); Medium: TMB score >=10 muts/mb and <20 muts/mb; Low: TMB score <10 muts/mb.
Time Frame At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this outcome measure was presented for Phase 2 only as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 42 5 22 23 20 11 40 21 18 9
Measure Type: Count of Participants
Unit of Measure: Participants
High
4
   9.5%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5
  12.5%
0
   0.0%
2
  11.1%
0
   0.0%
Medium
9
  21.4%
1
  20.0%
3
  13.6%
2
   8.7%
1
   5.0%
2
  18.2%
4
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
Low
13
  31.0%
3
  60.0%
12
  54.5%
20
  87.0%
12
  60.0%
6
  54.5%
22
  55.0%
11
  52.4%
13
  72.2%
8
  88.9%
Unknown
16
  38.1%
0
   0.0%
7
  31.8%
1
   4.3%
7
  35.0%
3
  27.3%
9
  22.5%
10
  47.6%
3
  16.7%
1
  11.1%
33.Secondary Outcome
Title Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline
Hide Description DDR defect positive was determined by presence of one or more pathogenic or likely pathogenic mutations in tissue, DNA and/or blood samples.
Time Frame At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this outcome measure was presented for Phase 2 only as pre-specified in reporting and analysis plan.
Arm/Group Title Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description:
Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/herman epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Overall Number of Participants Analyzed 42 5 22 23 20 11 40 21 18 9
Measure Type: Count of Participants
Unit of Measure: Participants
Positive
12
  28.6%
3
  60.0%
10
  45.5%
19
  82.6%
5
  25.0%
10
  90.9%
18
  45.0%
7
  33.3%
16
  88.9%
8
  88.9%
Negative
30
  71.4%
2
  40.0%
12
  54.5%
4
  17.4%
15
  75.0%
1
   9.1%
22
  55.0%
13
  61.9%
2
  11.1%
1
  11.1%
Unknown
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
Time Frame All-cause mortality: From start of the treatment up to 90 days post last dose of study treatment (maximum of 5.2 years approximately), TEAEs and Serious TEAEs: from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first (maximum of 5.2 years approximately).
Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. Safety set was evaluated. The safety analysis set included all participants who received at least 1 dose of study drug. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
 
Arm/Group Title Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Hide Arm/Group Description Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally once daily (QD) in combination with avelumab 800 mg intravenously (IV) every 2 weeks (Q2W) for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
All-Cause Mortality
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/12 (50.00%)   33/42 (78.57%)   3/5 (60.00%)   16/22 (72.73%)   16/23 (69.57%)   11/20 (55.00%)   6/11 (54.55%)   26/40 (65.00%)   16/21 (76.19%)   14/18 (77.78%)   7/9 (77.78%) 
Hide Serious Adverse Events
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/12 (8.33%)   16/42 (38.10%)   2/5 (40.00%)   7/22 (31.82%)   5/23 (21.74%)   9/20 (45.00%)   2/11 (18.18%)   16/40 (40.00%)   5/21 (23.81%)   9/18 (50.00%)   4/9 (44.44%) 
Blood and lymphatic system disorders                       
Anaemia * 1  1/12 (8.33%)  2/42 (4.76%)  0/5 (0.00%)  3/22 (13.64%)  2/23 (8.70%)  0/20 (0.00%)  0/11 (0.00%)  3/40 (7.50%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Autoimmune neutropenia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Immune thrombocytopenia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Thrombocytopenia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  2/9 (22.22%) 
Cardiac disorders                       
Acute myocardial infarction * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Atrial fibrillation * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Atrial thrombosis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Cardiac failure * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Cardiopulmonary failure * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Myocarditis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Endocrine disorders                       
Glucocorticoid deficiency * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Gastrointestinal disorders                       
Abdominal pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Abdominal pain upper * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Colitis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Constipation * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Diarrhoea * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Melaena * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Nausea * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Subileus * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Vomiting * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
General disorders                       
Disease progression * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  2/22 (9.09%)  1/23 (4.35%)  2/20 (10.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  2/9 (22.22%) 
Face oedema * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Fatigue * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Oedema peripheral * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Pyrexia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  2/40 (5.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Suprapubic pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Infections and infestations                       
Bronchitis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Cellulitis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Lower respiratory tract infection * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Pneumonia * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Upper respiratory tract infection * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Urinary tract infection * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  2/40 (5.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Urosepsis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Injury, poisoning and procedural complications                       
Accidental overdose * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Hyphaema * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Infusion related reaction * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Subdural haemorrhage * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Investigations                       
Blood bilirubin increased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Blood creatine phosphokinase increased * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Blood creatinine increased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Blood thyroid stimulating hormone increased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Platelet count decreased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Metabolism and nutrition disorders                       
Hyperglycaemia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Hyponatraemia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Musculoskeletal and connective tissue disorders                       
Back pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Coccydynia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Osteonecrosis of jaw * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                       
Lung neoplasm malignant * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Malignant neoplasm progression * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Neoplasm progression * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Nervous system disorders                       
Dizziness * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Spinal cord compression * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Renal and urinary disorders                       
Acute kidney injury * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Anuria * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Haematuria * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  4/40 (10.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Haemorrhage urinary tract * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Reproductive system and breast disorders                       
Female genital tract fistula * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Testicular pain * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Vaginal haemorrhage * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Respiratory, thoracic and mediastinal disorders                       
Acute respiratory distress syndrome * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Chronic obstructive pulmonary disease * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Dyspnoea * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Pulmonary embolism * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Respiratory distress * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Vascular disorders                       
Circulatory collapse * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Deep vein thrombosis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Embolism * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Haematoma * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Venous thrombosis limb * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
1
Term from vocabulary, MedDRA v25.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Phase 2: Cohort A1 (NSCLC) Phase 2: Cohort A2 (NSCLC DDR+) Phase 2: Cohort B1 (TNBC) Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Phase 2: Cohort C1 (OVC) Phase 2: Cohort C2 (OVC BRCA-mutated) Phase 2: Cohort D (UC) Phase 2: Cohort E1 (mCRPC) Phase 2: Cohort E2 (mCRPC DDR+) Phase 2: Cohort F (BRCA/ATM-mutated)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   41/42 (97.62%)   5/5 (100.00%)   21/22 (95.45%)   22/23 (95.65%)   20/20 (100.00%)   10/11 (90.91%)   38/40 (95.00%)   21/21 (100.00%)   16/18 (88.89%)   9/9 (100.00%) 
Blood and lymphatic system disorders                       
Anaemia * 1  8/12 (66.67%)  28/42 (66.67%)  4/5 (80.00%)  18/22 (81.82%)  10/23 (43.48%)  12/20 (60.00%)  7/11 (63.64%)  31/40 (77.50%)  15/21 (71.43%)  10/18 (55.56%)  5/9 (55.56%) 
Leukopenia * 1  0/12 (0.00%)  7/42 (16.67%)  0/5 (0.00%)  3/22 (13.64%)  1/23 (4.35%)  4/20 (20.00%)  0/11 (0.00%)  5/40 (12.50%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Lymphadenopathy * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Lymphopenia * 1  0/12 (0.00%)  5/42 (11.90%)  0/5 (0.00%)  4/22 (18.18%)  0/23 (0.00%)  5/20 (25.00%)  0/11 (0.00%)  4/40 (10.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Neutropenia * 1  7/12 (58.33%)  10/42 (23.81%)  2/5 (40.00%)  6/22 (27.27%)  4/23 (17.39%)  4/20 (20.00%)  2/11 (18.18%)  6/40 (15.00%)  3/21 (14.29%)  0/18 (0.00%)  2/9 (22.22%) 
Thrombocytopenia * 1  5/12 (41.67%)  15/42 (35.71%)  1/5 (20.00%)  9/22 (40.91%)  2/23 (8.70%)  9/20 (45.00%)  4/11 (36.36%)  16/40 (40.00%)  6/21 (28.57%)  3/18 (16.67%)  2/9 (22.22%) 
Cardiac disorders                       
Atrial fibrillation * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Palpitations * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Sinus tachycardia * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  2/20 (10.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Congenital, familial and genetic disorders                       
Hypophosphatasia * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Ear and labyrinth disorders                       
Ear congestion * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Vertigo * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Endocrine disorders                       
Glucocorticoid deficiency * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Hyperthyroidism * 1  0/12 (0.00%)  3/42 (7.14%)  1/5 (20.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Hypothyroidism * 1  1/12 (8.33%)  2/42 (4.76%)  1/5 (20.00%)  0/22 (0.00%)  3/23 (13.04%)  2/20 (10.00%)  1/11 (9.09%)  1/40 (2.50%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Immune-mediated hypothyroidism * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Eye disorders                       
Diplopia * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Ocular hyperaemia * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Vision blurred * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Gastrointestinal disorders                       
Abdominal discomfort * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Abdominal distension * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  5/20 (25.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  2/9 (22.22%) 
Abdominal pain * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  1/22 (4.55%)  2/23 (8.70%)  3/20 (15.00%)  3/11 (27.27%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  3/9 (33.33%) 
Abdominal pain lower * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  3/20 (15.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Abdominal pain upper * 1  0/12 (0.00%)  6/42 (14.29%)  0/5 (0.00%)  1/22 (4.55%)  1/23 (4.35%)  2/20 (10.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Ascites * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Constipation * 1  1/12 (8.33%)  6/42 (14.29%)  3/5 (60.00%)  5/22 (22.73%)  4/23 (17.39%)  3/20 (15.00%)  4/11 (36.36%)  7/40 (17.50%)  5/21 (23.81%)  2/18 (11.11%)  2/9 (22.22%) 
Diarrhoea * 1  0/12 (0.00%)  8/42 (19.05%)  1/5 (20.00%)  2/22 (9.09%)  5/23 (21.74%)  7/20 (35.00%)  3/11 (27.27%)  7/40 (17.50%)  4/21 (19.05%)  4/18 (22.22%)  3/9 (33.33%) 
Dry mouth * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  2/22 (9.09%)  1/23 (4.35%)  0/20 (0.00%)  2/11 (18.18%)  2/40 (5.00%)  1/21 (4.76%)  1/18 (5.56%)  1/9 (11.11%) 
Dyspepsia * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  3/11 (27.27%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Dysphagia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Flatulence * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Gastritis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Gastrointestinal pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Gastrooesophageal reflux disease * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Gingival bleeding * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Lip dry * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Lip swelling * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Mouth ulceration * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Nausea * 1  0/12 (0.00%)  14/42 (33.33%)  0/5 (0.00%)  10/22 (45.45%)  11/23 (47.83%)  14/20 (70.00%)  6/11 (54.55%)  12/40 (30.00%)  8/21 (38.10%)  6/18 (33.33%)  2/9 (22.22%) 
Noninfective gingivitis * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Oral pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Proctalgia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Stomatitis * 1  1/12 (8.33%)  2/42 (4.76%)  1/5 (20.00%)  1/22 (4.55%)  3/23 (13.04%)  1/20 (5.00%)  2/11 (18.18%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Subileus * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Tongue discolouration * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Tongue pigmentation * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Vomiting * 1  0/12 (0.00%)  4/42 (9.52%)  0/5 (0.00%)  4/22 (18.18%)  6/23 (26.09%)  4/20 (20.00%)  4/11 (36.36%)  2/40 (5.00%)  6/21 (28.57%)  3/18 (16.67%)  2/9 (22.22%) 
General disorders                       
Asthenia * 1  0/12 (0.00%)  8/42 (19.05%)  0/5 (0.00%)  2/22 (9.09%)  2/23 (8.70%)  4/20 (20.00%)  0/11 (0.00%)  4/40 (10.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Chest pain * 1  0/12 (0.00%)  3/42 (7.14%)  1/5 (20.00%)  0/22 (0.00%)  2/23 (8.70%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Chills * 1  5/12 (41.67%)  7/42 (16.67%)  0/5 (0.00%)  0/22 (0.00%)  4/23 (17.39%)  4/20 (20.00%)  2/11 (18.18%)  4/40 (10.00%)  3/21 (14.29%)  2/18 (11.11%)  2/9 (22.22%) 
Facial pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Fatigue * 1  2/12 (16.67%)  17/42 (40.48%)  4/5 (80.00%)  8/22 (36.36%)  10/23 (43.48%)  11/20 (55.00%)  8/11 (72.73%)  14/40 (35.00%)  10/21 (47.62%)  5/18 (27.78%)  6/9 (66.67%) 
Influenza like illness * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  0/11 (0.00%)  3/40 (7.50%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Localised oedema * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Mucosal inflammation * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  2/11 (18.18%)  2/40 (5.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Non-cardiac chest pain * 1  0/12 (0.00%)  5/42 (11.90%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  0/20 (0.00%)  2/11 (18.18%)  3/40 (7.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Oedema peripheral * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  2/20 (10.00%)  2/11 (18.18%)  3/40 (7.50%)  3/21 (14.29%)  2/18 (11.11%)  4/9 (44.44%) 
Peripheral swelling * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  1/23 (4.35%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Pyrexia * 1  0/12 (0.00%)  7/42 (16.67%)  0/5 (0.00%)  2/22 (9.09%)  4/23 (17.39%)  2/20 (10.00%)  3/11 (27.27%)  8/40 (20.00%)  2/21 (9.52%)  4/18 (22.22%)  0/9 (0.00%) 
Hepatobiliary disorders                       
Jaundice * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Immune system disorders                       
Seasonal allergy * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Infections and infestations                       
Balanitis candida * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
COVID-19 * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Candida infection * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Cystitis * 1  1/12 (8.33%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Herpes zoster * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Localised infection * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Lower respiratory tract infection * 1  0/12 (0.00%)  3/42 (7.14%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Nasopharyngitis * 1  0/12 (0.00%)  3/42 (7.14%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Oral candidiasis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Pneumonia * 1  0/12 (0.00%)  5/42 (11.90%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  3/40 (7.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Sinusitis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  1/9 (11.11%) 
Skin infection * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  1/22 (4.55%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Upper respiratory tract infection * 1  0/12 (0.00%)  0/42 (0.00%)  2/5 (40.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Urinary tract infection * 1  1/12 (8.33%)  2/42 (4.76%)  0/5 (0.00%)  1/22 (4.55%)  2/23 (8.70%)  1/20 (5.00%)  1/11 (9.09%)  6/40 (15.00%)  0/21 (0.00%)  2/18 (11.11%)  2/9 (22.22%) 
Vulvovaginal mycotic infection * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Injury, poisoning and procedural complications                       
Contusion * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  2/23 (8.70%)  3/20 (15.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Fall * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  2/23 (8.70%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  1/18 (5.56%)  2/9 (22.22%) 
Infusion related reaction * 1  1/12 (8.33%)  4/42 (9.52%)  0/5 (0.00%)  1/22 (4.55%)  1/23 (4.35%)  1/20 (5.00%)  1/11 (9.09%)  6/40 (15.00%)  4/21 (19.05%)  2/18 (11.11%)  2/9 (22.22%) 
Limb injury * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Muscle injury * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Soft tissue injury * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Spinal fracture * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Investigations                       
Activated partial thromboplastin time prolonged * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  2/9 (22.22%) 
Alanine aminotransferase increased * 1  0/12 (0.00%)  2/42 (4.76%)  1/5 (20.00%)  1/22 (4.55%)  2/23 (8.70%)  4/20 (20.00%)  2/11 (18.18%)  2/40 (5.00%)  2/21 (9.52%)  0/18 (0.00%)  1/9 (11.11%) 
Amylase decreased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Amylase increased * 1  1/12 (8.33%)  3/42 (7.14%)  2/5 (40.00%)  1/22 (4.55%)  1/23 (4.35%)  3/20 (15.00%)  1/11 (9.09%)  1/40 (2.50%)  3/21 (14.29%)  2/18 (11.11%)  1/9 (11.11%) 
Aspartate aminotransferase increased * 1  1/12 (8.33%)  1/42 (2.38%)  2/5 (40.00%)  1/22 (4.55%)  2/23 (8.70%)  3/20 (15.00%)  2/11 (18.18%)  1/40 (2.50%)  3/21 (14.29%)  1/18 (5.56%)  1/9 (11.11%) 
Blood albumin decreased * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  2/20 (10.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Blood alkaline phosphatase increased * 1  1/12 (8.33%)  9/42 (21.43%)  1/5 (20.00%)  3/22 (13.64%)  2/23 (8.70%)  3/20 (15.00%)  1/11 (9.09%)  4/40 (10.00%)  3/21 (14.29%)  2/18 (11.11%)  3/9 (33.33%) 
Blood bilirubin increased * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  1/21 (4.76%)  1/18 (5.56%)  2/9 (22.22%) 
Blood calcium decreased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Blood creatine phosphokinase increased * 1  0/12 (0.00%)  1/42 (2.38%)  1/5 (20.00%)  1/22 (4.55%)  1/23 (4.35%)  3/20 (15.00%)  2/11 (18.18%)  1/40 (2.50%)  2/21 (9.52%)  0/18 (0.00%)  0/9 (0.00%) 
Blood creatinine increased * 1  2/12 (16.67%)  1/42 (2.38%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  4/20 (20.00%)  0/11 (0.00%)  7/40 (17.50%)  4/21 (19.05%)  3/18 (16.67%)  1/9 (11.11%) 
Blood lactate dehydrogenase increased * 1  0/12 (0.00%)  4/42 (9.52%)  0/5 (0.00%)  3/22 (13.64%)  0/23 (0.00%)  4/20 (20.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Blood magnesium decreased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  4/20 (20.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Blood urea increased * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  2/20 (10.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Blood uric acid increased * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  3/20 (15.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Creatinine renal clearance decreased * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  2/20 (10.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Electrocardiogram QT prolonged * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/12 (0.00%)  5/42 (11.90%)  1/5 (20.00%)  3/22 (13.64%)  0/23 (0.00%)  3/20 (15.00%)  1/11 (9.09%)  3/40 (7.50%)  2/21 (9.52%)  2/18 (11.11%)  4/9 (44.44%) 
International normalised ratio increased * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Lipase increased * 1  1/12 (8.33%)  4/42 (9.52%)  1/5 (20.00%)  1/22 (4.55%)  1/23 (4.35%)  4/20 (20.00%)  1/11 (9.09%)  2/40 (5.00%)  3/21 (14.29%)  1/18 (5.56%)  3/9 (33.33%) 
Lymphocyte count decreased * 1  1/12 (8.33%)  1/42 (2.38%)  1/5 (20.00%)  2/22 (9.09%)  3/23 (13.04%)  3/20 (15.00%)  0/11 (0.00%)  3/40 (7.50%)  4/21 (19.05%)  2/18 (11.11%)  2/9 (22.22%) 
Neutrophil count decreased * 1  2/12 (16.67%)  2/42 (4.76%)  0/5 (0.00%)  1/22 (4.55%)  3/23 (13.04%)  5/20 (25.00%)  10/11 (90.91%)  5/40 (12.50%)  3/21 (14.29%)  2/18 (11.11%)  1/9 (11.11%) 
Platelet count decreased * 1  1/12 (8.33%)  3/42 (7.14%)  1/5 (20.00%)  4/22 (18.18%)  4/23 (17.39%)  5/20 (25.00%)  7/11 (63.64%)  7/40 (17.50%)  8/21 (38.10%)  7/18 (38.89%)  2/9 (22.22%) 
SARS-CoV-2 test positive * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Weight decreased * 1  1/12 (8.33%)  2/42 (4.76%)  1/5 (20.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Weight increased * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
White blood cell count decreased * 1  4/12 (33.33%)  1/42 (2.38%)  0/5 (0.00%)  1/22 (4.55%)  1/23 (4.35%)  4/20 (20.00%)  1/11 (9.09%)  9/40 (22.50%)  4/21 (19.05%)  5/18 (27.78%)  1/9 (11.11%) 
Metabolism and nutrition disorders                       
Decreased appetite * 1  1/12 (8.33%)  18/42 (42.86%)  2/5 (40.00%)  4/22 (18.18%)  3/23 (13.04%)  5/20 (25.00%)  1/11 (9.09%)  5/40 (12.50%)  5/21 (23.81%)  6/18 (33.33%)  4/9 (44.44%) 
Dehydration * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  2/20 (10.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  3/9 (33.33%) 
Hypercalcaemia * 1  1/12 (8.33%)  1/42 (2.38%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  1/40 (2.50%)  1/21 (4.76%)  1/18 (5.56%)  1/9 (11.11%) 
Hyperglycaemia * 1  2/12 (16.67%)  3/42 (7.14%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  4/20 (20.00%)  0/11 (0.00%)  4/40 (10.00%)  2/21 (9.52%)  2/18 (11.11%)  2/9 (22.22%) 
Hyperkalaemia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  2/40 (5.00%)  2/21 (9.52%)  0/18 (0.00%)  0/9 (0.00%) 
Hypermagnesaemia * 1  1/12 (8.33%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  2/21 (9.52%)  0/18 (0.00%)  0/9 (0.00%) 
Hyperuricaemia * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Hypoalbuminaemia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  5/40 (12.50%)  2/21 (9.52%)  2/18 (11.11%)  2/9 (22.22%) 
Hypocalcaemia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  3/40 (7.50%)  2/21 (9.52%)  2/18 (11.11%)  0/9 (0.00%) 
Hypokalaemia * 1  2/12 (16.67%)  2/42 (4.76%)  2/5 (40.00%)  2/22 (9.09%)  2/23 (8.70%)  2/20 (10.00%)  1/11 (9.09%)  3/40 (7.50%)  2/21 (9.52%)  2/18 (11.11%)  0/9 (0.00%) 
Hypomagnesaemia * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  3/20 (15.00%)  3/11 (27.27%)  2/40 (5.00%)  0/21 (0.00%)  3/18 (16.67%)  0/9 (0.00%) 
Hyponatraemia * 1  0/12 (0.00%)  0/42 (0.00%)  2/5 (40.00%)  1/22 (4.55%)  0/23 (0.00%)  1/20 (5.00%)  2/11 (18.18%)  4/40 (10.00%)  1/21 (4.76%)  2/18 (11.11%)  2/9 (22.22%) 
Hypophosphataemia * 1  2/12 (16.67%)  3/42 (7.14%)  1/5 (20.00%)  1/22 (4.55%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  4/40 (10.00%)  2/21 (9.52%)  2/18 (11.11%)  1/9 (11.11%) 
Vitamin D deficiency * 1  0/12 (0.00%)  1/42 (2.38%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Musculoskeletal and connective tissue disorders                       
Arthralgia * 1  0/12 (0.00%)  6/42 (14.29%)  0/5 (0.00%)  2/22 (9.09%)  6/23 (26.09%)  2/20 (10.00%)  2/11 (18.18%)  8/40 (20.00%)  2/21 (9.52%)  4/18 (22.22%)  1/9 (11.11%) 
Back pain * 1  0/12 (0.00%)  7/42 (16.67%)  1/5 (20.00%)  1/22 (4.55%)  8/23 (34.78%)  5/20 (25.00%)  2/11 (18.18%)  5/40 (12.50%)  4/21 (19.05%)  2/18 (11.11%)  1/9 (11.11%) 
Bone pain * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  1/23 (4.35%)  1/20 (5.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Flank pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  2/22 (9.09%)  2/23 (8.70%)  3/20 (15.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  1/18 (5.56%)  0/9 (0.00%) 
Groin pain * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Muscle spasms * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  3/11 (27.27%)  1/40 (2.50%)  2/21 (9.52%)  2/18 (11.11%)  1/9 (11.11%) 
Muscular weakness * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  2/11 (18.18%)  0/40 (0.00%)  4/21 (19.05%)  0/18 (0.00%)  1/9 (11.11%) 
Musculoskeletal chest pain * 1  1/12 (8.33%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Musculoskeletal discomfort * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Myalgia * 1  0/12 (0.00%)  3/42 (7.14%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  3/11 (27.27%)  1/40 (2.50%)  1/21 (4.76%)  2/18 (11.11%)  0/9 (0.00%) 
Myositis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Osteonecrosis of jaw * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Osteoporosis * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Pain in extremity * 1  0/12 (0.00%)  3/42 (7.14%)  0/5 (0.00%)  0/22 (0.00%)  2/23 (8.70%)  4/20 (20.00%)  1/11 (9.09%)  3/40 (7.50%)  2/21 (9.52%)  1/18 (5.56%)  0/9 (0.00%) 
Tendon disorder * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                       
Basal cell carcinoma * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Squamous cell carcinoma * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Tumour pain * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Nervous system disorders                       
Disturbance in attention * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Dizziness * 1  0/12 (0.00%)  8/42 (19.05%)  1/5 (20.00%)  1/22 (4.55%)  2/23 (8.70%)  4/20 (20.00%)  2/11 (18.18%)  3/40 (7.50%)  2/21 (9.52%)  3/18 (16.67%)  1/9 (11.11%) 
Dysgeusia * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  3/22 (13.64%)  2/23 (8.70%)  0/20 (0.00%)  5/11 (45.45%)  2/40 (5.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Headache * 1  0/12 (0.00%)  7/42 (16.67%)  0/5 (0.00%)  4/22 (18.18%)  4/23 (17.39%)  2/20 (10.00%)  4/11 (36.36%)  3/40 (7.50%)  2/21 (9.52%)  2/18 (11.11%)  1/9 (11.11%) 
Memory impairment * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Neuropathy peripheral * 1  2/12 (16.67%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  2/11 (18.18%)  0/40 (0.00%)  1/21 (4.76%)  1/18 (5.56%)  0/9 (0.00%) 
Somnolence * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  2/9 (22.22%) 
Spinal cord compression * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Syncope * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  1/18 (5.56%)  0/9 (0.00%) 
Tremor * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  2/20 (10.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Psychiatric disorders                       
Anxiety * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  2/22 (9.09%)  0/23 (0.00%)  2/20 (10.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Confusional state * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Depressed mood * 1  0/12 (0.00%)  1/42 (2.38%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Depression * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  2/23 (8.70%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Hallucination * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Insomnia * 1  0/12 (0.00%)  2/42 (4.76%)  1/5 (20.00%)  2/22 (9.09%)  2/23 (8.70%)  2/20 (10.00%)  1/11 (9.09%)  2/40 (5.00%)  2/21 (9.52%)  1/18 (5.56%)  0/9 (0.00%) 
Mood altered * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Restlessness * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Renal and urinary disorders                       
Acute kidney injury * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  3/40 (7.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Dysuria * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Haematuria * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  2/20 (10.00%)  0/11 (0.00%)  6/40 (15.00%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Hydronephrosis * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Nocturia * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Pollakiuria * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  1/21 (4.76%)  1/18 (5.56%)  0/9 (0.00%) 
Proteinuria * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Urinary incontinence * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Reproductive system and breast disorders                       
Pelvic pain * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Vulvovaginal dryness * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Vulvovaginal pruritus * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Respiratory, thoracic and mediastinal disorders                       
Cough * 1  1/12 (8.33%)  8/42 (19.05%)  0/5 (0.00%)  2/22 (9.09%)  2/23 (8.70%)  2/20 (10.00%)  3/11 (27.27%)  7/40 (17.50%)  1/21 (4.76%)  4/18 (22.22%)  1/9 (11.11%) 
Dysphonia * 1  0/12 (0.00%)  4/42 (9.52%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Dyspnoea * 1  0/12 (0.00%)  17/42 (40.48%)  1/5 (20.00%)  9/22 (40.91%)  2/23 (8.70%)  7/20 (35.00%)  3/11 (27.27%)  8/40 (20.00%)  2/21 (9.52%)  2/18 (11.11%)  2/9 (22.22%) 
Nasal congestion * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  1/22 (4.55%)  2/23 (8.70%)  1/20 (5.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Oropharyngeal pain * 1  1/12 (8.33%)  2/42 (4.76%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  3/20 (15.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Pharyngeal erythema * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Productive cough * 1  0/12 (0.00%)  5/42 (11.90%)  0/5 (0.00%)  1/22 (4.55%)  1/23 (4.35%)  0/20 (0.00%)  2/11 (18.18%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Pulmonary embolism * 1  0/12 (0.00%)  3/42 (7.14%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  2/20 (10.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Pulmonary haemorrhage * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Rhinorrhoea * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  2/11 (18.18%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Sinus congestion * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Skin and subcutaneous tissue disorders                       
Alopecia * 1  1/12 (8.33%)  2/42 (4.76%)  1/5 (20.00%)  3/22 (13.64%)  3/23 (13.04%)  3/20 (15.00%)  3/11 (27.27%)  1/40 (2.50%)  0/21 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Ecchymosis * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Erythema * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Night sweats * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  1/20 (5.00%)  1/11 (9.09%)  1/40 (2.50%)  1/21 (4.76%)  0/18 (0.00%)  0/9 (0.00%) 
Petechiae * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Pruritus * 1  0/12 (0.00%)  5/42 (11.90%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  2/20 (10.00%)  2/11 (18.18%)  3/40 (7.50%)  0/21 (0.00%)  3/18 (16.67%)  1/9 (11.11%) 
Rash * 1  1/12 (8.33%)  2/42 (4.76%)  0/5 (0.00%)  2/22 (9.09%)  0/23 (0.00%)  1/20 (5.00%)  0/11 (0.00%)  3/40 (7.50%)  0/21 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Rash erythematous * 1  0/12 (0.00%)  0/42 (0.00%)  1/5 (20.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Rash maculo-papular * 1  0/12 (0.00%)  3/42 (7.14%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  1/20 (5.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Skin hyperpigmentation * 1  1/12 (8.33%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Skin ulcer * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Vascular disorders                       
Deep vein thrombosis * 1  1/12 (8.33%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Embolism * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  1/18 (5.56%)  1/9 (11.11%) 
Flushing * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Haematoma * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Hot flush * 1  1/12 (8.33%)  1/42 (2.38%)  0/5 (0.00%)  0/22 (0.00%)  1/23 (4.35%)  2/20 (10.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Hypertension * 1  0/12 (0.00%)  2/42 (4.76%)  0/5 (0.00%)  1/22 (4.55%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  1/21 (4.76%)  1/18 (5.56%)  0/9 (0.00%) 
Hypotension * 1  0/12 (0.00%)  1/42 (2.38%)  0/5 (0.00%)  3/22 (13.64%)  1/23 (4.35%)  1/20 (5.00%)  0/11 (0.00%)  1/40 (2.50%)  1/21 (4.76%)  0/18 (0.00%)  1/9 (11.11%) 
Lymphoedema * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  2/22 (9.09%)  1/23 (4.35%)  0/20 (0.00%)  0/11 (0.00%)  1/40 (2.50%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Orthostatic hypotension * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  0/11 (0.00%)  0/40 (0.00%)  0/21 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Peripheral coldness * 1  0/12 (0.00%)  0/42 (0.00%)  0/5 (0.00%)  0/22 (0.00%)  0/23 (0.00%)  0/20 (0.00%)  1/11 (9.09%)  0/40 (0.00%)  0/21 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
1
Term from vocabulary, MedDRA v25.1
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03330405    
Other Study ID Numbers: B9991025
2017-001509-33 ( EudraCT Number )
JAVELIN PARP MEDLEY ( Other Identifier: Alias Study Number )
First Submitted: October 16, 2017
First Posted: November 6, 2017
Results First Submitted: February 10, 2023
Results First Posted: June 12, 2023
Last Update Posted: October 13, 2023