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CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

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: NCT03123783
Recruitment Status : Completed
First Posted : April 21, 2017
Results First Posted : December 5, 2023
Last Update Posted : December 26, 2023
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Apexigen America, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cancer
Non Small Cell Lung Cancer Metastatic
Metastatic Melanoma
Neoplasm of Lung
Melanoma
Interventions Drug: APX005M
Drug: Nivolumab
Enrollment 140
Recruitment Details

In Phase 1b dose-escalation portion of the study, a total of 10 participants were enrolled at 3 dose levels. Nine participants received at least one dose of both study drugs. 0.3 mg/kg was determined as the recommended phase 2 (RP2D) dose.

Note: The 3 participants treated in DL3 of Phase 1b are at the RP2D and are also included in Phase 2 results. One participant was rolled over to Cohort 1 (Phase 2) and 2 participants were rolled over into Cohort 2 (Phase 2) to continue treatment.
Pre-assignment Details For the phase 2 cohorts 1,2,3A,3B, a total of 133 participants were enrolled in 4 cohorts to receive APX005M at 0.3 mg/kg (RP2D) plus nivolumab at 360 mg IV. Three subjects who were treated at the RP2D in the Phase 1b dose-escalation portion of the study were included in Phase 2 of the relevant disease-specific cohort. The study enrollment was completed as planned and all primary and secondary outcome measures and adverse events were collected even though the study was ended by the sponsor.
Arm/Group Title DL1 - APX005M 0.03 mg/kg + Nivolumab (Phase 1b) DL2 - APX005M 0.1 mg/kg + Nivolumab (Phase 1b) DL3 - APX005M 0.3 mg/kg + Nivolumab (Phase 1b) Cohort 1(Arm)/ inNSCLC (Phase 2) Cohort 2(Arm)/ PD1-MM (Phase 2) - Cohort 3A(Arm)/ PD1-NSCLC (Phase 2) Cohort 3B(Arm)/ PD1-NSCLC (Phase 2)
Hide Arm/Group Description Participants received 0.03mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg Participants received 0.1mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Period Title: Phase 1b
Started 3 4 3 0 0 0 0
Participants in the Safety Population 3 3 3 0 0 0 0
Participants in the Efficacy Population 3 3 3 0 0 0 0
Completed [1] 3 3 0 0 0 0 0
Not Completed 0 1 3 0 0 0 0
Reason Not Completed
Removed from treatment prior to APX005M administration             0             1             0             0             0             0             0
Participants rolled over to Phase 2             0             0             3             0             0             0             0
[1]
Participants completed Ph1b who did not receive RP2D did not roll over to Phase 2
Period Title: Phase 2
Started [1] 0 0 0 53 38 14 28
Phase 2 Participants in Safety Population 0 0 0 53 38 14 28
Phase 2 Participants in the Efficacy (EE) Population 0 0 0 48 33 12 25
Completed 0 0 0 48 33 12 25
Not Completed 0 0 0 5 5 2 3
Reason Not Completed
No post baseline tumor assesment on treatment period             0             0             0             5             2             2             3
Prior systemic therapy not allowed (1 patient did not complete post baseline tumor assessment)             0             0             0             0             3             0             0
[1]
Only 3 participants in Phase 1b rolled over to Phase 2 study
Arm/Group Title DL1 - APX005M 0.03 mg/kg + Nivolumab (Phase 1b) DL2 - APX005M 0.1 mg/kg + Nivolumab (Phase 1b) DL3 - APX005M 0.3 mg/kg + Nivolumab (Phase 1b) Cohort 1(Arm)/ inNSCLC (Phase 2) Cohort 2(Arm)/ PD1-MM (Phase 2) Cohort 3A(Arm)/ PD1-NSCLC (Phase 2) Cohort 3B(Arm)/ PD1-NSCLC (Phase 2) Total
Hide Arm/Group Description Participants received 0.03 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.1 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Total of all reporting groups
Overall Number of Baseline Participants 3 4 3 52 36 14 28 140
Hide Baseline Analysis Population Description
Phase 1b: immunotherapy naïve metastatic or locally advanced NSCLC (inNSCLC) or unresectable or metastatic melanoma (MM) Phase 2: Cohort 1/inNSCLC, Cohort 2/unresec or MM that progressed during treatment with anti-PD-1/PD-L1, Cohort 3/PD1-NSCLC metastatic or locally advanced NSCLC not amenable to curative treatment that progressed during prior treatment with anti-PD-1/PD-L1. Cohort 3A: best response of PD or with SD <16 wks, Cohort 3B includes PD1-NSCLC with tumor response or with SD ≥ 16 wks.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1b Age, Categorical Number Analyzed 3 participants 4 participants 3 participants 0 participants 0 participants 0 participants 0 participants 10 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Between 18 and 65 years
1
  33.3%
3
  75.0%
2
  66.7%
 0 0 0 0
6
  60.0%
>=65 years
2
  66.7%
1
  25.0%
1
  33.3%
 0 0 0 0
4
  40.0%
Phase 2 Age, Categorical Number Analyzed 0 participants 0 participants 0 participants 52 participants 36 participants 14 participants 28 participants 130 participants
<=18 years 0 0 0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years 0 0 0
17
  32.7%
19
  52.8%
5
  35.7%
15
  53.6%
56
  43.1%
>=65 years 0 0 0
35
  67.3%
17
  47.2%
9
  64.3%
13
  46.4%
74
  56.9%
[1]
Measure Analysis Population Description: The participants were enrolled into multiple Arms/Groups and are reported in the Arm/Group they were originally assigned.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1b Number Analyzed 3 participants 4 participants 3 participants 0 participants 0 participants 0 participants 0 participants 10 participants
Female
0
   0.0%
1
  25.0%
1
  33.3%
 0 0 0 0
2
  20.0%
Male
3
 100.0%
3
  75.0%
2
  66.7%
 0 0 0 0
8
  80.0%
Phase 2 Number Analyzed 0 participants 0 participants 0 participants 52 participants 36 participants 14 participants 28 participants 130 participants
Female 0 0 0
21
  40.4%
15
  41.7%
5
  35.7%
9
  32.1%
50
  38.5%
Male 0 0 0
31
  59.6%
21
  58.3%
9
  64.3%
19
  67.9%
80
  61.5%
[1]
Measure Analysis Population Description: The participants were enrolled into multiple Arms/Groups and are reported in the Arm/Group they were originally assigned
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1b Number Analyzed 3 participants 4 participants 3 participants 0 participants 0 participants 0 participants 0 participants 10 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Not Hispanic or Latino
3
 100.0%
4
 100.0%
3
 100.0%
 0 0 0 0
10
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Phase 2 Number Analyzed 0 participants 0 participants 0 participants 52 participants 36 participants 14 participants 28 participants 130 participants
Hispanic or Latino 0 0 0
10
  19.2%
4
  11.1%
3
  21.4%
4
  14.3%
21
  16.2%
Not Hispanic or Latino 0 0 0
42
  80.8%
32
  88.9%
11
  78.6%
24
  85.7%
109
  83.8%
Unknown or Not Reported 0 0 0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: The participants were enrolled into multiple Arms/Groups and are reported in the Arm/Group they were originally assigned
Race (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1b Number Analyzed 3 participants 4 participants 3 participants 0 participants 0 participants 0 participants 0 participants 10 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Black or African American
0
   0.0%
1
  25.0%
0
   0.0%
 0 0 0 0
1
  10.0%
White
3
 100.0%
3
  75.0%
3
 100.0%
 0 0 0 0
9
  90.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0
0
   0.0%
Phase 2 Number Analyzed 0 participants 0 participants 0 participants 52 participants 36 participants 14 participants 28 participants 130 participants
American Indian or Alaska Native 0 0 0
0
   0.0%
1
   2.8%
0
   0.0%
0
   0.0%
1
   0.8%
Asian 0 0 0
1
   1.9%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.8%
Native Hawaiian or Other Pacific Islander 0 0 0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American 0 0 0
3
   5.8%
0
   0.0%
0
   0.0%
1
   3.6%
4
   3.1%
White 0 0 0
48
  92.3%
35
  97.2%
14
 100.0%
27
  96.4%
124
  95.4%
More than one race 0 0 0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported 0 0 0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: The participants were enrolled into multiple Arms/Groups and are reported in the Arm/Group they were originally assigned
[2]
Measure Analysis Population Description: The participants were enrolled into multiple Arms/Groups and are reported in the Arm/Group they were originally assigned
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 4 participants 3 participants 52 participants 36 participants 14 participants 28 participants 140 participants
3 4 3 34 20 6 6 76
Spain Number Analyzed 3 participants 4 participants 3 participants 52 participants 36 participants 14 participants 28 participants 140 participants
0 0 0 18 16 8 22 64
Weight   [1] 
Mean (Full Range)
Unit of measure:  Kg
Phase 1b Number Analyzed 3 participants 4 participants 3 participants 0 participants 0 participants 0 participants 0 participants 10 participants
85.3
(67.4 to 112.5)
84.33
(64.7 to 107.0)
104.3
(93.4 to 118.4)
90.63
(64.7 to 118.4)
Phase 2 Number Analyzed 0 participants 0 participants 0 participants 52 participants 36 participants 14 participants 28 participants 130 participants
76.53
(50.26 to 106.59)
80.15
(34.06 to 171.10)
74.42
(55.00 to 95.60)
71.80
(48.80 to 129.30)
76.29
(34.06 to 171.10)
[1]
Measure Analysis Population Description: The participants were enrolled into multiple Arms/Groups and are reported in the Arm/Group they were originally assigned
ECOG Performance Status   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1b Number Analyzed 3 participants 4 participants 3 participants 0 participants 0 participants 0 participants 0 participants 10 participants
ECOG Score 0
1
  33.3%
1
  25.0%
3
 100.0%
5
  50.0%
ECOG Score 1
2
  66.7%
3
  75.0%
0
   0.0%
5
  50.0%
Phase 2 Number Analyzed 0 participants 0 participants 0 participants 52 participants 36 participants 14 participants 28 participants 130 participants
ECOG Score 0 0 0 0
13
  25.0%
28
  77.8%
7
  50.0%
8
  28.6%
56
  43.1%
ECOG Score 1 0 0 0
39
  75.0%
8
  22.2%
7
  50.0%
20
  71.4%
74
  56.9%
[1]
Measure Description:

Grade 0 - Normal activity, fully active, able to carry on all pre-disease performance without restriction Grade 1 - Symptoms, but fully ambulatory, restricted in physically strenuous but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work)

Grade 0 is better than Grade 1.

[2]
Measure Analysis Population Description: The participants were enrolled into multiple Arms/Groups and are reported in the Arm/Group they were originally assigned
1.Primary Outcome
Title Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Hide Description

All toxicities were graded according to the NCI-CTCAE version 4.03. DLT was defined as any of the following events attributed to APX005M and nivolumab combination:

  • Grade 4 hematologic toxicity lasting ≥ 7 days (except asymptomatic lymphopenia)
  • Grade 3 or 4 neutropenia with a single temperature of >38.3◦ C (101◦ F) or a sustained temperature of ≥38◦ C (100.4◦ F) for more than one hour
  • Grade 4 thrombocytopenia or Grade ≥3 thrombocytopenia with signs or symptoms of bleeding or requiring platelet transfusion
  • Grade 4 non-hematologic toxicity
  • Grade 3 non-hematologic toxicity lasting >3 days despite optimal supportive care
  • Any Grade ≥ 3 non-hematologic laboratory value if: medical intervention is required to treat the subject, abnormality leads to hospitalization, or abnormality persists for >1 week
  • Failure to recover from a treatment-related AE to baseline or ≤ Grade 1 within 12 weeks of last dose of investigational product
  • Grade 5 toxicity.
Time Frame Up to 21 days following first dose of APX005M and nivolumab
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the safety population who received at least 1 dose of study drug in the escalation cohorts (APX005M 0.03 mg/kg + nivolumab; APX005M 0.1 mg/kg + nivolumab; APX005M 0.3 mg/kg + nivolumab)
Arm/Group Title Phase 1b Escalation
Hide Arm/Group Description:
Participants received intravenous infusions of APX005M starting at DL 0.03, .1 or .3 mg/kg administered every 21 days in combination with nivolumab 360 mg IV
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Primary Outcome
Title Maximum Tolerated Dose (MTD) of APX005M + Nivolumab (Phase 1b)
Hide Description Establish the MTD dose of APX005M combined with 360 mg of nivolumab for which for which < 33% of DLT- evaluable participants experience a DLT. In Phase 1b, the RP2D was based on the overall safety and tolerability of the combination of APX005M and nivolumab by testing increasing doses up to 0.3 mg/kg APX005M + nivolumab.
Time Frame Up to 21 days following first dose of APX005M and nivolumab
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the safety population who received at least 1 dose of study drug in the escalation cohorts (APX005M 0.03 mg/kg + nivolumab; APX005M 0.1 mg/kg + nivolumab; APX005M 0.3 mg/kg + nivolumab)
Arm/Group Title Phase 1b Escalation
Hide Arm/Group Description:
Participants received intravenous infusions of APX005M starting at DL 0.03, .1 or .3 mg/kg administered every 21 days in combination with nivolumab 360 mg IV
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: mg/kg
NA [1] 
[1]
The MTD was formally not reached.
3.Primary Outcome
Title Phase 2 Evaluate the Objective Response Rate (ORR) by RECIST 1.1 and iRECIST in Each Cohort / Group
Hide Description ORR defined as the rate of patients who show as best overall response; either a complete response (CR) or a partial response (PR). The ORR can be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. using computed tomography (CT) scans/magnetic resonance imaging (MRI). Per RECIST v1.1, for target lesions and assessed by imaging: Complete Response, (CR), Disappearance of all target lesions and nontarget (NT) lesions; Partial Response (PR), >30% decrease in the sum of the longest diameter of target lesions and no PD in NT lesions or new lesions; Objective Response Rate (ORR)=CR + PR.
Time Frame From start of the treatment (Day 1) until disease progression, withdrawal of consent, death, initiation of any anticancer therapy, lost to follow-up, or termination by the Sponsor, whichever comes first (for Phase 2: maximum up to 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 weeks, Cohort 3: PD1-NSCLC metastatic or locally advanced NSCLC not amenable to curative treatment that progressed during prior treatment with anti-PD-1/PD-L1 therapy. Cohort 3A: best response of PD or with SD <16 weeks, Cohort 3B includes PD1-NSCLC with tumor response or with SD ≥ 16 weeks
Arm/Group Title Cohort 1 (Arm)/inNSCLC (Phase 2) Cohort 2(Arm)/PD1-MM (Phase 2) Cohort 3A(Arm)/PD1-NSCLC (Phase 2) Cohort 3B(Arm)/PD1-NSCLC (Phase 2)
Hide Arm/Group Description:
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Overall Number of Participants Analyzed 48 33 12 25
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
16.67
(8.57 to 28.07)
15.15
(6.17 to 29.25)
0.00
(0.00 to 22.09)
0.00
(0.00 to 11.29)
4.Secondary Outcome
Title Safety of the APX005M and Nivolumab Combination (Phase 2)
Hide Description Number of participants with TEAEs are reported.
Time Frame Day 1 up to 30 days (or 100 days for SAEs and AEs with potential immunologic etiology) following the after the last dose of APX005M and/or nivolumab (from start of treatment up to 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Any Adverse Event a participant has with two or more events in that category is counted only once
Arm/Group Title Cohort 1 (Arm)/inNSCLC (Phase 2) Cohort 2(Arm)/PD1-MM (Phase 2) Cohort 3A(Arm)/PD1-NSCLC (Phase 2) Cohort 3B(Arm)/PD1-NSCLC (Phase 2)
Hide Arm/Group Description:
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Overall Number of Participants Analyzed 53 38 14 28
Measure Type: Count of Participants
Unit of Measure: Participants
52
  98.1%
36
  94.7%
14
 100.0%
28
 100.0%
5.Secondary Outcome
Title Duration of Response (DOR) as Per RECIST 1.1(Phase 2)
Hide Description Duration of Response is defined as the time from the first evidence of confirmed partial response (PR) or better by Per RECIST v1.1 to disease progression or death due to any cause; in subjects alive without progressive disease (PD), DOR was censored on the date of the last tumor assessment. PD is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Maximum up to 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 week. Cohort 3A/PD1-NSCLC and Cohort 3B/PD1 NSCLC had no objective response and therefore DOR could not be assessed.
Arm/Group Title Cohort 1(Arm)/inNSCLC (Phase 2) Cohort 2(Arm)/PD1-MM (Phase 2)
Hide Arm/Group Description:
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Overall Number of Participants Analyzed 8 5
Median (Full Range)
Unit of Measure: Months
NA [1] 
(3.9 to 21.4)
NA [2] 
(4.2 to 24.7)
[1]
NA because median duration of response not reached.
[2]
NA because median duration of response not reached. 4/5 participants had ongoing responses at the time of study closure.
6.Secondary Outcome
Title Median Progression-free Survival (PFS) (Phase 2)
Hide Description Progression-free Survival (PFS) in each cohort, measured from first dose to the earlier of PD (by RECIST 1.1) or death due to any cause, whichever occurs first.
Time Frame From start of treatment (Day 1) up to 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 weeks, Cohort 3: PD1-NSCLC metastatic or locally advanced NSCLC not amenable to curative treatment that progressed during prior treatment with anti-PD-1/PD-L1 therapy. Cohort 3A: best response of PD or with SD <16 weeks, Cohort 3B includes PD1-NSCLC with tumor response or with SD ≥ 16 weeks.
Arm/Group Title Cohort 1(Arm)/inNSCLC (Phase 2) Cohort 2(Arm)/PD1-MM (Phase 2) Cohort 3A(Arm)/PD1-NSCLC (Phase 2) Cohort 3B(Arm)/PD1-NSCLC (Phase 2)
Hide Arm/Group Description:
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Overall Number of Participants Analyzed 48 33 12 25
Median (90% Confidence Interval)
Unit of Measure: Months
4.11
(3.45 to 5.52)
1.97
(1.87 to 3.61)
3.43
(2.00 to 3.88)
3.65
(1.84 to 3.81)
7.Secondary Outcome
Title 6-month PFS Rate (Phase 2)
Hide Description PFS rate in each cohort, measured from first dose to the earlier of PD (by RECIST 1.1) or death due to any cause, whichever occurs first.
Time Frame * Outcome Measure Time Frame From start of treatment (Day 1) to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 weeks, Cohort 3: PD1-NSCLC metastatic or locally advanced NSCLC not amenable to curative treatment that progressed during prior treatment with anti-PD-1/PD-L1 therapy. Cohort 3A: best response of PD or with SD <16 weeks, Cohort 3B includes PD1-NSCLC with tumor response or with SD ≥ 16 weeks.
Arm/Group Title Cohort 1(Arm)/inNSCLC (Phase 2) Cohort 2(Arm)/PD1-MM (Phase 2) Cohort 3A(Arm)/PD1-NSCLC (Phase 2) Cohort 3B(Arm)/PD1-NSCLC (Phase 2)
Hide Arm/Group Description:
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
Overall Number of Participants Analyzed 48 33 12 25
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
33.10
(20.10 to 46.68)
21.21
(9.35 to 36.25)
25.00
(6.01 to 50.48)
12.92
(3.27 to 29.41)
Time Frame Day 1 through 30 days (or 100 days for SAEs and AEs with potential immunologic etiology) after the last dose of study drug (up to 27 months)
Adverse Event Reporting Description

An AE considered "serious" (SAE) if, in the view of either the Investigator or sponsor, it results in any of the following outcomes:

  • Death
  • A life-threatening AE
  • Inpatient hospitalization or prolongation of existing hospitalization
  • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
  • A congenital anomaly/birth defect
 
Arm/Group Title DL1 - APX005M 0.03 mg/kg + Nivolumab (Phase 1b Escalation) DL2 - APX005M 0.1 mg/kg + Nivolumab (Phase 1b Escalation) DL3 - APX005M 0.3 mg/kg + Nivolumab (Phase 1b Escalation) Cohort 1(Arm)/ inNSCLC (Phase 2) - Includes Data From 1 Participant From DL3 Cohort 2(Arm)/ PD1-MM (Phase 2) - Includes Data From 2 Participants From DL3 Cohort 3A(Arm)/ PD1-NSCLC (Phase 2) Cohort 3B(Arm)/ PD1-NSCLC (Phase 2)
Hide Arm/Group Description Participants received 0.03 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.1 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV

Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV

Note: One participant was rolled over to Cohort 1 (Phase 2) and 2 participants were rolled over into Cohort 2 (Phase 2).

 Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV Participants received 0.3 mg/kg of APX005M administered every 21 days in combination with nivolumab 360 mg IV
All-Cause Mortality
DL1 - APX005M 0.03 mg/kg + Nivolumab (Phase 1b Escalation) DL2 - APX005M 0.1 mg/kg + Nivolumab (Phase 1b Escalation) DL3 - APX005M 0.3 mg/kg + Nivolumab (Phase 1b Escalation) Cohort 1(Arm)/ inNSCLC (Phase 2) - Includes Data From 1 Participant From DL3 Cohort 2(Arm)/ PD1-MM (Phase 2) - Includes Data From 2 Participants From DL3 Cohort 3A(Arm)/ PD1-NSCLC (Phase 2) Cohort 3B(Arm)/ PD1-NSCLC (Phase 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)      1/3 (33.33%)      0/3 (0.00%)      18/53 (33.96%)      4/38 (10.53%)      4/14 (28.57%)      9/28 (32.14%)    
Hide Serious Adverse Events
DL1 - APX005M 0.03 mg/kg + Nivolumab (Phase 1b Escalation) DL2 - APX005M 0.1 mg/kg + Nivolumab (Phase 1b Escalation) DL3 - APX005M 0.3 mg/kg + Nivolumab (Phase 1b Escalation) Cohort 1(Arm)/ inNSCLC (Phase 2) - Includes Data From 1 Participant From DL3 Cohort 2(Arm)/ PD1-MM (Phase 2) - Includes Data From 2 Participants From DL3 Cohort 3A(Arm)/ PD1-NSCLC (Phase 2) Cohort 3B(Arm)/ PD1-NSCLC (Phase 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      1/3 (33.33%)      0/3 (0.00%)      25/53 (47.17%)      6/38 (15.79%)      6/14 (42.86%)      13/28 (46.43%)    
Cardiac disorders               
Acute coronary syndrome †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Acute myocardial infarction †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Cardiac arrest †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Cardio-respiratory arrest †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Pericardial effusion †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Eye disorders               
Optic ischaemic neuropathy †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Gastrointestinal disorders               
Constipation †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Gastritis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Intestinal obstruction †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Pancreatitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Pancreatitis acute †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Colitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
General disorders               
Facial pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
General physical health deterioration †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Pyrexia †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Immune system disorders               
Cytokine release syndrome †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 2/28 (7.14%)  2
Infections and infestations               
Appendicitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Bacteraemia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 1/28 (3.57%)  1
Bronchitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Infuenza †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Lung abscess †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Lung infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Pneumonia †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 4/53 (7.55%)  5 0/38 (0.00%)  0 2/14 (14.29%)  2 2/28 (7.14%)  2
Sepsis †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Streptococcal bacteraemia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Injury, poisoning and procedural complications               
Fall †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Femur fracture †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Hip fracture †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Radius fracture †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Toxicity to various agents †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Investigations               
Blood bilirubin increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Weight decreased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Metabolism and nutrition disorders               
Diabetic ketoacidosis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Hypercalcaemia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Hyperglycaemia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders               
Arthralgia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Back pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Myositis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Bone neoplasm †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Cancer pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 1/28 (3.57%)  1
Nervous system disorders               
Brain oedema †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Cerebrovascular accident †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Encephalitis autoimmune †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Seizure †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Syncope †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Psychiatric disorders               
Confusional state †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Renal and urinary disorders               
Acute kidney injury †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Acute respiratory failure †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Chronic obstructive pulmonary disease †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  4 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Chronic respiratory failure †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Dyspnoea †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 1/14 (7.14%)  1 2/28 (7.14%)  2
Pleural effusion †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Pneumothorax †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Pulmonary artery thrombosis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Pulmonary embolism †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 0/38 (0.00%)  0 1/14 (7.14%)  1 2/28 (7.14%)  2
Respiratory failure †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Vascular disorders               
Deep vein thrombosis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DL1 - APX005M 0.03 mg/kg + Nivolumab (Phase 1b Escalation) DL2 - APX005M 0.1 mg/kg + Nivolumab (Phase 1b Escalation) DL3 - APX005M 0.3 mg/kg + Nivolumab (Phase 1b Escalation) Cohort 1(Arm)/ inNSCLC (Phase 2) - Includes Data From 1 Participant From DL3 Cohort 2(Arm)/ PD1-MM (Phase 2) - Includes Data From 2 Participants From DL3 Cohort 3A(Arm)/ PD1-NSCLC (Phase 2) Cohort 3B(Arm)/ PD1-NSCLC (Phase 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      52/53 (98.11%)      36/38 (94.74%)      14/14 (100.00%)      28/28 (100.00%)    
Blood and lymphatic system disorders               
Anaemia †  0/3 (0.00%)  0 2/3 (66.67%)  2 0/3 (0.00%)  0 13/53 (24.53%)  31 4/38 (10.53%)  8 0/14 (0.00%)  0 6/28 (21.43%)  10
Lymph node pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Cardiac disorders               
Palpitations †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 2/38 (5.26%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Sinus tachycardia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 1/38 (2.63%)  1 0/14 (0.00%)  0 1/28 (3.57%)  1
Tachycardia †  0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 7/53 (13.21%)  7 2/38 (5.26%)  2 1/14 (7.14%)  1 2/28 (7.14%)  2
Atrial Fibrillation †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Pericardial effusion †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Ear and labyrinth disorders               
Ear Pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/53 (1.89%)  1 2/38 (5.26%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Vertigo †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/53 (0.00%)  0 2/38 (5.26%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Endocrine disorders               
Hyperthyroidism †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  4 1/38 (2.63%)  1 0/14 (0.00%)  0 1/28 (3.57%)  1
Hypothyroidism †  1/3 (33.33%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 5/53 (9.43%)  5 2/38 (5.26%)  2 1/14 (7.14%)  1 0/28 (0.00%)  0
Eye disorders               
Vision blurred †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 1/38 (2.63%)  1 1/14 (7.14%)  1 0/28 (0.00%)  0
Vitreous floaters †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Asthenopia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Dry Eye †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 1/14 (7.14%)  1 0/28 (0.00%)  0
Eye Pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Retinal exudates †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Gastrointestinal disorders               
Abdominal pain †  0/3 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 3/53 (5.66%)  7 2/38 (5.26%)  2 2/14 (14.29%)  3 0/28 (0.00%)  0
Abdominal pain upper †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  3 3/14 (21.43%)  3 1/28 (3.57%)  1
Constipation †  1/3 (33.33%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 10/53 (18.87%)  15 5/38 (13.16%)  5 3/14 (21.43%)  3 0/28 (0.00%)  0
Diarrhoea †  0/3 (0.00%)  0 1/3 (33.33%)  1 2/3 (66.67%)  3 12/53 (22.64%)  37 6/38 (15.79%)  8 2/14 (14.29%)  8 2/28 (7.14%)  2
Dry mouth †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 6/53 (11.32%)  6 2/38 (5.26%)  2 2/14 (14.29%)  2 1/28 (3.57%)  1
Dyspepsia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 2/38 (5.26%)  3 0/14 (0.00%)  0 0/28 (0.00%)  0
Dysphagia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 2/28 (7.14%)  2
Nausea †  1/3 (33.33%)  1 1/3 (33.33%)  7 3/3 (100.00%)  5 24/53 (45.28%)  54 18/38 (47.37%)  22 7/14 (50.00%)  13 8/28 (28.57%)  13
Odynophagia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 2/28 (7.14%)  2
Stomatitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  5 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Vomiting †  1/3 (33.33%)  1 2/3 (66.67%)  3 3/3 (100.00%)  4 18/53 (33.96%)  46 10/38 (26.32%)  19 2/14 (14.29%)  3 5/28 (17.86%)  8
Toothache †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 1/14 (7.14%)  1 0/28 (0.00%)  0
General disorders               
Asthenia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 7/53 (13.21%)  8 6/38 (15.79%)  10 4/14 (28.57%)  6 12/28 (42.86%)  17
Chest discomfort †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 2/14 (14.29%)  2 0/28 (0.00%)  0
Chest pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 1/38 (2.63%)  1 0/14 (0.00%)  0 5/28 (17.86%)  8
Chills †  0/3 (0.00%)  0 2/3 (66.67%)  3 3/3 (100.00%)  5 30/53 (56.60%)  65 19/38 (50.00%)  51 5/14 (35.71%)  14 13/28 (46.43%)  24
Fatigue †  3/3 (100.00%)  4 2/3 (66.67%)  8 0/3 (0.00%)  0 18/53 (33.96%)  41 15/38 (39.47%)  36 5/14 (35.71%)  12 4/28 (14.29%)  4
Malaise †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 2/53 (3.77%)  2 4/38 (10.53%)  4 3/14 (21.43%)  3 0/28 (0.00%)  0
Non-cardiac chest pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 5/53 (9.43%)  5 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Oedema peripheral †  0/3 (0.00%)  0 2/3 (66.67%)  4 0/3 (0.00%)  0 4/53 (7.55%)  7 3/38 (7.89%)  3 3/14 (21.43%)  3 2/28 (7.14%)  2
Pain †  1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 5/53 (9.43%)  6 1/38 (2.63%)  1 0/14 (0.00%)  0 1/28 (3.57%)  1
Pyrexia †  0/3 (0.00%)  0 2/3 (66.67%)  3 2/3 (66.67%)  4 28/53 (52.83%)  56 26/38 (68.42%)  57 7/14 (50.00%)  34 12/28 (42.86%)  24
Influenza like illness †  0/3 (0.00%)  0 0/3 (0.00%)  0 2/3 (66.67%)  2 2/53 (3.77%)  2 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Discomfort †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 1/28 (3.57%)  1
Performance status decreased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Hepatobiliary disorders               
Autoimmune hepatitis †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Immune system disorders               
Cytokine release syndrome †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 3/53 (5.66%)  4 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Hypersensitivity †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Infections and infestations               
Nasopharyngitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 1/38 (2.63%)  1 0/14 (0.00%)  0 2/28 (7.14%)  2
Pneumonia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 6/53 (11.32%)  8 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Respiratory tract infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 4/28 (14.29%)  4
Sinusitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  3 0/38 (0.00%)  0 0/14 (0.00%)  0 2/28 (7.14%)  2
Upper respiratory tract infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  3 4/38 (10.53%)  4 2/14 (14.29%)  2 0/28 (0.00%)  0
Urinary tract infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 2/38 (5.26%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Fungal infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Localised infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/53 (1.89%)  1 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Lung infection †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Skin infection †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/53 (1.89%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Anorectal infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Candida infection †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Gingivitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Herpes zoster †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  2 0/38 (0.00%)  0 1/14 (7.14%)  1 1/28 (3.57%)  1
Pharygitis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 1/28 (3.57%)  1
Injury, poisoning and procedural complications               
Fall †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  6 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Infusion related reaction †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 5/53 (9.43%)  6 3/38 (7.89%)  4 2/14 (14.29%)  2 3/28 (10.71%)  6
Contusion †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Ligament sprain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Investigations               
Alanine aminotransferase increased †  0/3 (0.00%)  0 1/3 (33.33%)  3 0/3 (0.00%)  0 11/53 (20.75%)  33 11/38 (28.95%)  19 4/14 (28.57%)  6 8/28 (28.57%)  34
Blood alkaline phosphatase †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 2/14 (14.29%)  2 0/28 (0.00%)  0
Blood alkaline phosphatase increased †  0/3 (0.00%)  0 1/3 (33.33%)  3 0/3 (0.00%)  0 9/53 (16.98%)  34 7/38 (18.42%)  12 1/14 (7.14%)  1 3/28 (10.71%)  5
Blood bilirubin increased †  1/3 (33.33%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 3/53 (5.66%)  4 3/38 (7.89%)  5 0/14 (0.00%)  0 1/28 (3.57%)  4
Blood creatinine increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 5/53 (9.43%)  8 1/38 (2.63%)  5 1/14 (7.14%)  2 1/28 (3.57%)  1
Blood lactate dehydrogenase increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 3/38 (7.89%)  3 0/14 (0.00%)  0 1/28 (3.57%)  2
Gamma-glutamyltransferase increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 8/53 (15.09%)  19 7/38 (18.42%)  18 4/14 (28.57%)  10 5/28 (17.86%)  15
Haemoglobin decreased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 1/38 (2.63%)  7 0/14 (0.00%)  0 3/28 (10.71%)  3
Lipase increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 5/53 (9.43%)  9 1/38 (2.63%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Platelet count decreased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  10 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Weight decreased †  0/3 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 14/53 (26.42%)  21 0/38 (0.00%)  0 1/14 (7.14%)  1 3/28 (10.71%)  3
Amylase increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  5 2/38 (5.26%)  4 1/14 (7.14%)  2 2/28 (7.14%)  3
Aspartate aminotransferase increased †  1/3 (33.33%)  1 1/3 (33.33%)  5 0/3 (0.00%)  0 12/53 (22.64%)  23 9/38 (23.68%)  16 4/14 (28.57%)  5 8/28 (28.57%)  17
Lymphocyte count decrease †  1/3 (33.33%)  1 1/3 (33.33%)  2 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Monocyte count decreased †  1/3 (33.33%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Blood cortisol decreased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Blood glucose increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  2 1/14 (7.14%)  2 0/28 (0.00%)  0
Blood urea increased †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Weight increased †  0/3 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Metabolism and nutrition disorders               
Decreased appetite †  1/3 (33.33%)  1 2/3 (66.67%)  9 1/3 (33.33%)  2 14/53 (26.42%)  15 4/38 (10.53%)  4 4/14 (28.57%)  5 7/28 (25.00%)  8
Dehydration †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 5/53 (9.43%)  10 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Hypercalcaemia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 2/28 (7.14%)  3
Hyperglycaemia †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 4/53 (7.55%)  4 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Hypokalaemia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  4 0/38 (0.00%)  0 0/14 (0.00%)  0 2/28 (7.14%)  5
Hypomagnesaemia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  3
Hyponatraemia †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  6 1/38 (2.63%)  1 0/14 (0.00%)  0 1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders               
Arthralgia †  1/3 (33.33%)  1 1/3 (33.33%)  1 1/3 (33.33%)  5 12/53 (22.64%)  23 6/38 (15.79%)  16 3/14 (21.43%)  3 5/28 (17.86%)  6
Back pain †  1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 8/53 (15.09%)  11 4/38 (10.53%)  6 1/14 (7.14%)  1 2/28 (7.14%)  2
Bone pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  3
Flank pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  2
Muscular weakness †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  4 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Musculoskeletal chest pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 2/38 (5.26%)  2 1/14 (7.14%)  1 1/28 (3.57%)  1
Musculoskeletal pain †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  4 1/38 (2.63%)  1 2/14 (14.29%)  2 2/28 (7.14%)  2
Myalgia †  0/3 (0.00%)  0 1/3 (33.33%)  2 1/3 (33.33%)  1 4/53 (7.55%)  4 6/38 (15.79%)  10 1/14 (7.14%)  2 1/28 (3.57%)  1
Neck pain †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  3 0/38 (0.00%)  0 1/14 (7.14%)  1 2/28 (7.14%)  2
Pain in extremity †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  3 3/38 (7.89%)  6 0/14 (0.00%)  0 5/28 (17.86%)  5
Muscle rigidity †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Ostenonecrosis of jaw †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Pain in jaw †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  2 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Nervous system disorders               
Dizziness †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 3/53 (5.66%)  3 2/38 (5.26%)  2 1/14 (7.14%)  1 0/28 (0.00%)  0
Dysgeusia †  1/3 (33.33%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 3/53 (5.66%)  4 2/38 (5.26%)  2 1/14 (7.14%)  1 0/28 (0.00%)  0
Headache †  1/3 (33.33%)  1 1/3 (33.33%)  2 1/3 (33.33%)  1 8/53 (15.09%)  13 8/38 (21.05%)  20 2/14 (14.29%)  4 4/28 (14.29%)  4
Somnolence †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 2/14 (14.29%)  2 0/28 (0.00%)  0
Hypoaesthesia †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Presyncope †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Lethargy †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Neuralgia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Tremor †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 1/38 (2.63%)  1 1/14 (7.14%)  1 1/28 (3.57%)  1
Vocal cord paralysis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Psychiatric disorders               
Anxiety †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 5/53 (9.43%)  5 1/38 (2.63%)  1 1/14 (7.14%)  1 0/28 (0.00%)  0
Confusional state †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  4 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Depression †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Insomnia †  0/3 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 13/53 (24.53%)  14 1/38 (2.63%)  1 1/14 (7.14%)  1 0/28 (0.00%)  0
Depressive symptom †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Disorientation †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Renal and urinary disorders               
Chromaturia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 2/38 (5.26%)  7 0/14 (0.00%)  0 0/28 (0.00%)  0
Dysuria †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 2/38 (5.26%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Haematuria †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Pollakiuria †  0/3 (0.00%)  0 1/3 (33.33%)  3 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Chronic obstructive pulmonary disease †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  7 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Cough †  1/3 (33.33%)  1 1/3 (33.33%)  1 1/3 (33.33%)  1 13/53 (24.53%)  16 3/38 (7.89%)  4 3/14 (21.43%)  3 10/28 (35.71%)  13
Dysphonia †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 2/38 (5.26%)  2 0/14 (0.00%)  0 1/28 (3.57%)  1
Dyspnoea †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 21/53 (39.62%)  30 3/38 (7.89%)  3 6/14 (42.86%)  8 8/28 (28.57%)  9
Dyspnoea exertional †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Epistaxis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  3 0/38 (0.00%)  0 0/14 (0.00%)  0 2/28 (7.14%)  3
Haemoptysis †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 3/53 (5.66%)  3 0/38 (0.00%)  0 1/14 (7.14%)  3 1/28 (3.57%)  1
Nasal congestion †  0/3 (0.00%)  0 1/3 (33.33%)  2 1/3 (33.33%)  1 1/53 (1.89%)  1 2/38 (5.26%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Pleural effusion †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 4/53 (7.55%)  4 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Pneumonitis †  1/3 (33.33%)  6 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 2/38 (5.26%)  4 0/14 (0.00%)  0 1/28 (3.57%)  2
Upper-airway cough syndrome †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 2/14 (14.29%)  2 0/28 (0.00%)  0
Wheezing †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 5/53 (9.43%)  6 1/38 (2.63%)  1 1/14 (7.14%)  1 1/28 (3.57%)  2
Dyspnoea at rest †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Hypoxia †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Lung infiltration †  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Productive cough †  1/3 (33.33%)  4 0/3 (0.00%)  0 0/3 (0.00%)  0 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Rhinorrhoea †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 2/53 (3.77%)  2 0/38 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1
Pulmonary embolism †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/53 (5.66%)  3 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Skin and subcutaneous tissue disorders               
Hyperhidrosis †  0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 3/53 (5.66%)  3 0/38 (0.00%)  0 2/14 (14.29%)  3 2/28 (7.14%)  3
Pruritus †  0/3 (0.00%)  0 1/3 (33.33%)  1 3/3 (100.00%)  3 16/53 (30.19%)  34 13/38 (34.21%)  15 4/14 (28.57%)  7 4/28 (14.29%)  7
Rash †  1/3 (33.33%)  2 1/3 (33.33%)  1 2/3 (66.67%)  3 9/53 (16.98%)  13 10/38 (26.32%)  13 1/14 (7.14%)  3 1/28 (3.57%)  1
Rash maculo-papular †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 4/53 (7.55%)  9 1/38 (2.63%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0
Blister †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Dry skin †  0/3 (0.00%)  0 2/3 (66.67%)  3 1/3 (33.33%)  1 2/53 (3.77%)  2 2/38 (5.26%)  2 0/14 (0.00%)  0 0/28 (0.00%)  0
Night sweats †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 2/53 (3.77%)  2 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Skin hypopigmentation †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0
Urticaria †  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/53 (1.89%)  1 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Lichenoid keratosis †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/53 (0.00%)  0 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Pruitus generalised †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/53 (1.89%)  1 0/38 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0
Vascular disorders               
Flushing †  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 6/53 (11.32%)  8 3/38 (7.89%)  3 0/14 (0.00%)  0 2/28 (7.14%)  2
Hypertension †  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 11/53 (20.75%)  16 2/38 (5.26%)  2 0/14 (0.00%)  0 3/28 (10.71%)  5
Hypotension †  0/3 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 10/53 (18.87%)  16 4/38 (10.53%)  5 1/14 (7.14%)  1 3/28 (10.71%)  4
†
Indicates events were collected by systematic assessment
In the AE section, DL3 participant data had no DLTs; AE data collected from DL3 was also added to Phase 2.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pyxis Oncology Clinical Operations
Organization: Pyxis Oncology, Inc.
Phone: (339) 545 8252
EMail: clinicaltrials@pyxisoncology.com
Layout table for additonal information
Responsible Party: Apexigen America, Inc.
ClinicalTrials.gov Identifier: NCT03123783    
Other Study ID Numbers: APX005M-002
First Submitted: April 17, 2017
First Posted: April 21, 2017
Results First Submitted: November 15, 2022
Results First Posted: December 5, 2023
Last Update Posted: December 26, 2023