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A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced 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: NCT03343054
Recruitment Status : Active, not recruiting
First Posted : November 17, 2017
Results First Posted : March 10, 2022
Last Update Posted : September 21, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Neoplasms
Breast Neoplasms
Intervention Drug: talazoparib
Enrollment 28
Recruitment Details This study included 2 periods: dose escalation and dose expansion. The recommended dose for dose expansion period of talazoparib was determined in dose escalation period.
Pre-assignment Details Dose escalation period: total 9 participants were screened, enrolled into the study and assigned to study treatment. Dose expansion period: total 22 participants were screened, out of which 3 participants were screen failure. 19 participants actually enrolled into the study and assigned to study treatment. Data reported based on the primary completion date of 11 January 2021.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 milligrams (mg) orally, once daily (QD) in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day minus (-) 7. Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7. Participants with Germline breast cancer susceptibility gene mutation (gBRCAm) HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Period Title: Dose Escalation Period (Up to 286 Days)
Started 3 6 0 [1]
Completed 0 0 0
Not Completed 3 6 0
Reason Not Completed
Progressive Disease             2             6             0
Global Deterioration of Health Status             1             0             0
[1]
Dose escalation and Dose expansion were separate populations.
Period Title: Dose Expansion Period (Up to 502 Days)
Started 0 0 19 [1]
Completed 0 0 0
Not Completed 0 0 19
Reason Not Completed
Progressive Disease             0             0             11
Ongoing             0             0             8
[1]
Dose escalation and Dose expansion were separate populations.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg Total
Hide Arm/Group Description Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7. Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7. Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days). Total of all reporting groups
Overall Number of Baseline Participants 3 6 19 28
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 3 participants 6 participants 19 participants 28 participants
Less than (<)18 Years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
18-44 Years
1
  33.3%
0
   0.0%
7
  36.8%
8
  28.6%
45-64 Years
1
  33.3%
3
  50.0%
6
  31.6%
10
  35.7%
Greater than or equal to (>=)65 Years
1
  33.3%
3
  50.0%
6
  31.6%
10
  35.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 19 participants 28 participants
Female
2
  66.7%
3
  50.0%
19
 100.0%
24
  85.7%
Male
1
  33.3%
3
  50.0%
0
   0.0%
4
  14.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 19 participants 28 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
3
 100.0%
6
 100.0%
19
 100.0%
28
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 19 participants 28 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
 100.0%
6
 100.0%
19
 100.0%
28
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
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%
1.Primary Outcome
Title Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT)
Hide Description DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (>)7days; Febrile neutropenia >1 hour; G greater than or equal to (>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for >=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)>5*upper limit of normal(ULN) and 2*increases above baseline values; ALT/AST>=3*ULN concurrent with total bilirubin (TB)>2*ULN; TB>5*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib.
Time Frame Cycle 1 (28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis set included all enrolled participants who received at least 1 dose of study treatment and who did not have major treatment deviations during the first cycle. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
Hide Description Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
57.9
(36.8 to 77.0)
3.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03
Hide Description Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as 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, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAS) included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 3 6 19
Measure Type: Count of Participants
Unit of Measure: Participants
3
 100.0%
6
 100.0%
19
 100.0%
4.Secondary Outcome
Title Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03
Hide Description A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. AE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Relatedness to study drug was assessed by the investigator.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 3 6 19
Measure Type: Count of Participants
Unit of Measure: Participants
2
  66.7%
3
  50.0%
19
 100.0%
5.Secondary Outcome
Title Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03
Hide Description AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by 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 AEs were reported.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 3 6 19
Measure Type: Count of Participants
Unit of Measure: Participants
1
  33.3%
2
  33.3%
11
  57.9%
6.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry
Hide Description Parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.
Time Frame Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 3 6 19
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase increased: Grade 1
1
  33.3%
2
  33.3%
8
  42.1%
Alanine aminotransferase increased: Grade 2
0
   0.0%
0
   0.0%
1
   5.3%
Alkaline phosphatase increased: Grade 1
1
  33.3%
2
  33.3%
4
  21.1%
Alkaline phosphatase increased: Grade 2
0
   0.0%
1
  16.7%
1
   5.3%
Aspartate aminotransferase increased: Grade 1
1
  33.3%
3
  50.0%
7
  36.8%
Blood bilirubin increased: Grade 1
0
   0.0%
0
   0.0%
2
  10.5%
Creatinine increased: Grade 1
2
  66.7%
6
 100.0%
17
  89.5%
Hyperglycemia: Grade 1
0
   0.0%
0
   0.0%
1
   5.3%
Hyperkalemia: Grade 1
1
  33.3%
0
   0.0%
0
   0.0%
Hypermagnesemia: Grade 1
0
   0.0%
0
   0.0%
1
   5.3%
Hypernatremia: Grade 1
0
   0.0%
1
  16.7%
1
   5.3%
Hypoalbuminemia: Grade 1
2
  66.7%
2
  33.3%
6
  31.6%
Hypoalbuminemia: Grade 2
0
   0.0%
1
  16.7%
0
   0.0%
Hypocalcemia: Grade 1
1
  33.3%
2
  33.3%
9
  47.4%
Hypoglycemia: Grade 1
0
   0.0%
0
   0.0%
1
   5.3%
Hypomagnesemia: Grade 1
0
   0.0%
1
  16.7%
2
  10.5%
Hyponatremia: Grade 1
1
  33.3%
1
  16.7%
2
  10.5%
Hypophosphatemia: Grade 2
1
  33.3%
1
  16.7%
2
  10.5%
7.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology
Hide Description Hematological parameters included: Anemia, Hemoglobin increased, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.
Time Frame Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 3 6 19
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia: Grade 1
3
 100.0%
2
  33.3%
8
  42.1%
Anemia: Grade 2
0
   0.0%
3
  50.0%
0
   0.0%
Anemia: Grade 3
0
   0.0%
1
  16.7%
9
  47.4%
Lymphocyte count decreased: Grade 1
1
  33.3%
2
  33.3%
6
  31.6%
Lymphocyte count decreased: Grade 2
2
  66.7%
3
  50.0%
4
  21.1%
Lymphocyte count decreased: Grade 3
0
   0.0%
1
  16.7%
2
  10.5%
Neutrophil count decreased: Grade 2
1
  33.3%
0
   0.0%
7
  36.8%
Neutrophil count decreased: Grade 3
0
   0.0%
1
  16.7%
4
  21.1%
Platelet count decreased: Grade 1
1
  33.3%
1
  16.7%
10
  52.6%
Platelet count decreased: Grade 2
0
   0.0%
1
  16.7%
1
   5.3%
White blood cell decreased: Grade 1
1
  33.3%
2
  33.3%
1
   5.3%
White blood cell decreased: Grade 2
1
  33.3%
1
  16.7%
9
  47.4%
White blood cell decreased: Grade 3
0
   0.0%
1
  16.7%
2
  10.5%
8.Secondary Outcome
Title Dose Escalation: Number of Participants With Abnormalities in Vital Signs
Hide Description Vital sign abnormalities: a) Sitting systolic blood pressure: <90 millimeter of mercury (mmHg), decrease from baseline >=30 mmHg, increase from baseline >=30 mmHg; b) Sitting diastolic blood pressure: minimum <50 mmHg, decrease from baseline >=20 mmHg, increase from baseline >=20 mmHg; c) Sitting pulse rate: minimum <40 beats per minute (bpm), maximum >120 bpm. Only those categories in which at least one participant had data were reported in this outcome measure.
Time Frame Baseline up to 286 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Measure Type: Count of Participants
Unit of Measure: Participants
Systolic blood pressure: <90 mmHg
1
  33.3%
0
   0.0%
Systolic blood pressure: decrease from baseline >=30 mmHg
0
   0.0%
2
  33.3%
9.Secondary Outcome
Title Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib
Hide Description Cmax was defined as the maximum observed plasma concentration of talazoparib.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
7.244
(34%)
13.78
(26%)
10.Secondary Outcome
Title Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib
Hide Description Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Median (Full Range)
Unit of Measure: Hours
0.983
(0.750 to 1.92)
0.967
(0.467 to 1.98)
11.Secondary Outcome
Title Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib
Hide Description Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram hour per milliliter
97.48
(17%)
159.1
(33%)
12.Secondary Outcome
Title Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib
Hide Description Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram hour per milliliter
46.55
(20%)
85.39
(44%)
13.Secondary Outcome
Title Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F)
Hide Description Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour
6.968
(12%)
5.010
(9%)
14.Secondary Outcome
Title Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib
Hide Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter
551.8
(42%)
361.1
(20%)
15.Secondary Outcome
Title Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib
Hide Description Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 4
Mean (Standard Deviation)
Unit of Measure: Hours
56.60  (17.860) 50.73  (10.121)
16.Secondary Outcome
Title Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib
Hide Description AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf).
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram hour per milliliter
107.5
(12%)
199.7
(9%)
17.Secondary Outcome
Title Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib
Hide Description Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
14.44
(26%)
32.84
(14%)
18.Secondary Outcome
Title Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib
Hide Description Pre dose plasma concentration of talazoparib.
Time Frame Pre dose on Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
2.175
(8%)
3.645
(49%)
19.Secondary Outcome
Title Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib
Hide Description Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose).
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Median (Full Range)
Unit of Measure: Hours
1.02
(0.967 to 1.87)
1.03
(0.733 to 1.92)
20.Secondary Outcome
Title Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib
Hide Description Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram hour per milliliter
127.2
(6%)
244.7
(21%)
21.Secondary Outcome
Title Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss)
Hide Description Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour
5.898
(7%)
4.086
(21%)
22.Secondary Outcome
Title Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib
Hide Description Accumulation ratio for AUC was calculated as AUCtau for Day 22 divided by AUCtau for Day -7, where AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours.
Time Frame Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day -7 and Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
2.734
(24%)
2.866
(64%)
23.Secondary Outcome
Title Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib
Hide Description Rss was calculated by dividing AUCtau at steady state (post multiple dosing on Day 22) by single dose AUCinf (on Day -7). AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Time Frame Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1; Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here "overall number of participants analyzed" signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
1.181
(12%)
1.249
(14%)
24.Secondary Outcome
Title Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Hide Description OR in participants was defined as the percentage of participants with CR or PR as best response determined by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Measure Type: Number
Unit of Measure: Percentage of participants
0 0
25.Secondary Outcome
Title Dose Escalation: Progression Free Survival (PFS)
Hide Description PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.
Time Frame From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 286 days)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 3 6
Median (95% Confidence Interval)
Unit of Measure: Months
3.0
(2.1 to 3.0)
3.4
(1.2 to 9.6)
26.Secondary Outcome
Title Dose Escalation: Duration of Response (DOR)
Hide Description DOR was defined as the time between the date of the first documented objective response (PR or CR) and the date of the first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to no participants with response in dose escalation period, data collection and analysis for DOR was not performed. Hence, data is not reported.
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7.
Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
27.Secondary Outcome
Title Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
Hide Description Confirmed OR in participants was defined as the percentage of participants with CR or PR as best response determined by BICR as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
52.6
(32.0 to 72.6)
28.Secondary Outcome
Title Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Hide Description Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.
Time Frame Baseline up to Week 16, Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
Up to Week 16
94.7
(77.4 to 99.7)
Up to Week 24
94.7
(77.4 to 99.7)
29.Secondary Outcome
Title Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
Hide Description Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by BICR as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.
Time Frame Baseline up to Week 16, Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
Up to Week 16
89.5
(70.4 to 98.1)
Up to Week 24
89.5
(70.4 to 98.1)
30.Secondary Outcome
Title Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Hide Description TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on subset of participants with OR. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 11
Median (Full Range)
Unit of Measure: Months
2.63
(1.2 to 9.4)
31.Secondary Outcome
Title Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
Hide Description TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by BICR according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on subset of participants with OR. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: Months
2.07
(1.2 to 4.2)
32.Secondary Outcome
Title Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Hide Description DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on subset of participants with OR.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 11
Median (95% Confidence Interval)
Unit of Measure: Months
6.8 [1] 
(2.7 to NA)
[1]
Upper limit of 95% confidence interval (CI) was not estimable due to low number of participants with event.
33.Secondary Outcome
Title Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
Hide Description DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on subset of participants with OR.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: Months
6.0 [1] 
(2.3 to NA)
[1]
Upper limit of 95% CI was not estimable due to low number of participants with event.
34.Secondary Outcome
Title Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Hide Description PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.
Time Frame From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: Months
7.2 [1] 
(4.1 to NA)
[1]
Upper limit of 95% CI was not estimable due to low number of participants with event.
35.Secondary Outcome
Title Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
Hide Description PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.
Time Frame From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: Months
7.2 [1] 
(3.9 to NA)
[1]
Upper limit of 95% CI was not estimable due to low number of participants with event.
36.Secondary Outcome
Title Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12
Hide Description OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at Month 12. Probability of participants who were event free at Month 12 was estimated by Kaplan-Meier method and reported.
Time Frame At Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability of event free participants
0.847
(0.575 to 0.951)
37.Secondary Outcome
Title Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib
Hide Description Pre dose plasma drug concentration.
Time Frame Pre dose at 0 hour on Day 1 of Cycle 2, 3, 4 and unplanned (any time during dose expansion period up to 502 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK concentration analysis set included all enrolled participants who were treated and have at least 1 analyte concentration. Here "number analyzed" signifies number of participants evaluated for given time point. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
Arm/Group Title Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description:
Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
Overall Number of Participants Analyzed 19
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram per milliliter
Cycle 2 Day 1 Number Analyzed 12 participants
3098
(40%)
Cycle 3 Day 1 Number Analyzed 13 participants
3423
(41%)
Cycle 4 Day 1 Number Analyzed 7 participants
2910
(52%)
Unplanned Number Analyzed 8 participants
3670
(38%)
Time Frame Dose escalation: maximum duration up to 286 days; Dose expansion: maximum duration up to 502 days
Adverse Event Reporting Description Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. 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. Safety set was evaluated.
 
Arm/Group Title Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Hide Arm/Group Description Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7. Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7. Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days).
All-Cause Mortality
Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)   0/6 (0.00%)   2/19 (10.53%) 
Hide Serious Adverse Events
Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)   0/6 (0.00%)   1/19 (5.26%) 
Hepatobiliary disorders       
Cholelithiasis * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Brain cancer metastatic * 1  1/3 (33.33%)  0/6 (0.00%)  0/19 (0.00%) 
1
Term from vocabulary, MedDRA v23.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dose Escalation: Talazoparib 0.75 mg Dose Escalation: Talazoparib 1.0 mg Dose Expansion: Talazoparib 1.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   6/6 (100.00%)   19/19 (100.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  0/3 (0.00%)  2/6 (33.33%)  13/19 (68.42%) 
Cardiac disorders       
Pericardial effusion * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Eye disorders       
Asthenopia * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Dry eye * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Gastrointestinal disorders       
Cheilitis * 1  0/3 (0.00%)  1/6 (16.67%)  2/19 (10.53%) 
Nausea * 1  0/3 (0.00%)  1/6 (16.67%)  5/19 (26.32%) 
Stomatitis * 1  0/3 (0.00%)  2/6 (33.33%)  7/19 (36.84%) 
Toothache * 1  0/3 (0.00%)  1/6 (16.67%)  1/19 (5.26%) 
Dental caries * 1  0/3 (0.00%)  1/6 (16.67%)  0/19 (0.00%) 
Abdominal pain * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Abdominal pain upper * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Ascites * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Constipation * 1  0/3 (0.00%)  0/6 (0.00%)  4/19 (21.05%) 
Diarrhoea * 1  0/3 (0.00%)  0/6 (0.00%)  2/19 (10.53%) 
Epigastric discomfort * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Gastritis * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Tooth loss * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Vomiting * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
General disorders       
Oedema peripheral * 1  0/3 (0.00%)  1/6 (16.67%)  0/19 (0.00%) 
Fatigue * 1  0/3 (0.00%)  0/6 (0.00%)  3/19 (15.79%) 
Malaise * 1  0/3 (0.00%)  0/6 (0.00%)  5/19 (26.32%) 
Pyrexia * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Infections and infestations       
Otitis media acute * 1  1/3 (33.33%)  0/6 (0.00%)  0/19 (0.00%) 
Sinusitis * 1  1/3 (33.33%)  0/6 (0.00%)  0/19 (0.00%) 
Conjunctivitis * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Nasopharyngitis * 1  0/3 (0.00%)  0/6 (0.00%)  2/19 (10.53%) 
Injury, poisoning and procedural complications       
Fall * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Rib fracture * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Tooth fracture * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Investigations       
Alanine aminotransferase increased * 1  1/3 (33.33%)  1/6 (16.67%)  1/19 (5.26%) 
Neutrophil count decreased * 1  1/3 (33.33%)  1/6 (16.67%)  12/19 (63.16%) 
Platelet count decreased * 1  0/3 (0.00%)  2/6 (33.33%)  6/19 (31.58%) 
White blood cell count decreased * 1  0/3 (0.00%)  1/6 (16.67%)  8/19 (42.11%) 
Aspartate aminotransferase increased * 1  0/3 (0.00%)  1/6 (16.67%)  0/19 (0.00%) 
Blood alkaline phosphatase increased * 1  1/3 (33.33%)  0/6 (0.00%)  0/19 (0.00%) 
Lymphocyte count decreased * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  0/3 (0.00%)  0/6 (0.00%)  2/19 (10.53%) 
Hyperglycaemia * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  1/3 (33.33%)  0/6 (0.00%)  1/19 (5.26%) 
Myalgia * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Pain in extremity * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumour pain * 1  1/3 (33.33%)  0/6 (0.00%)  0/19 (0.00%) 
Nervous system disorders       
Dysgeusia * 1  1/3 (33.33%)  0/6 (0.00%)  2/19 (10.53%) 
Dizziness * 1  0/3 (0.00%)  0/6 (0.00%)  3/19 (15.79%) 
Headache * 1  0/3 (0.00%)  0/6 (0.00%)  4/19 (21.05%) 
Paralysis recurrent laryngeal nerve * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders       
Sputum increased * 1  0/3 (0.00%)  1/6 (16.67%)  0/19 (0.00%) 
Cough * 1  0/3 (0.00%)  0/6 (0.00%)  2/19 (10.53%) 
Dyspnoea * 1  0/3 (0.00%)  0/6 (0.00%)  2/19 (10.53%) 
Oropharyngeal pain * 1  0/3 (0.00%)  0/6 (0.00%)  2/19 (10.53%) 
Skin and subcutaneous tissue disorders       
Rash maculo-papular * 1  0/3 (0.00%)  2/6 (33.33%)  1/19 (5.26%) 
Dyshidrotic eczema * 1  0/3 (0.00%)  1/6 (16.67%)  0/19 (0.00%) 
Alopecia * 1  0/3 (0.00%)  0/6 (0.00%)  6/19 (31.58%) 
Dermatitis contact * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Dry skin * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Nail pigmentation * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Pain of skin * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Pruritus * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Rash * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Urticaria * 1  0/3 (0.00%)  0/6 (0.00%)  1/19 (5.26%) 
Vascular disorders       
Essential hypertension * 1  0/3 (0.00%)  1/6 (16.67%)  0/19 (0.00%) 
1
Term from vocabulary, MedDRA v23.1
*
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
Layout table for Results Point of Contact information
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: NCT03343054    
Other Study ID Numbers: C3441030
First Submitted: November 11, 2017
First Posted: November 17, 2017
Results First Submitted: December 20, 2021
Results First Posted: March 10, 2022
Last Update Posted: September 21, 2023