Trial Outcomes & Findings for Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors (NCT NCT03565991)

Last Updated: 2023-09-25

Results Overview

For participants with solid tumors, except metastatic Castration Resistant Prostate Cancer (mCRPC), OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), both confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. For participants with mCRPC, OR was defined as the percentage of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria. Per RECIST v1.1, CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Non-target PR lesions must be non-Progressive Disease (PD), where PD was unequivocal progression of pre-existing lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

202 participants

Primary outcome timeframe

From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to approximately 24 months

Results posted on

2023-09-25

Participant Flow

A total of 270 participants were screened for this study, 202 participants were enrolled and assigned to study treatment but 2 participants never started the treatment. In total 200 participants were treated (159 in Cohort 1 and 41 in Cohort 2).

Participant milestones

Participant milestones
Measure	Cohort 1 (BReast CAncer Gene [BRCA] 1/2 Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg Once Daily (QD) for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour Intravenous (IV) infusion Every 2 Weeks (Q2W) on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (Ataxia Telangiectasia Mutated [ATM] Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Overall Study STARTED	159	41
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	158	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 (BReast CAncer Gene [BRCA] 1/2 Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg Once Daily (QD) for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour Intravenous (IV) infusion Every 2 Weeks (Q2W) on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (Ataxia Telangiectasia Mutated [ATM] Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Overall Study Other	11	0
Overall Study Global deterioration of health status	14	4
Overall Study Withdrawal by Subject	2	6
Overall Study Progressive disease	121	29
Overall Study Death	3	0
Overall Study Adverse Event	7	2

Baseline Characteristics

Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (BRCA 1/2 Defect) n=159 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) n=41 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Total n=200 Participants Total of all reporting groups
Age, Continuous	57.35 Years STANDARD_DEVIATION 12.88 • n=5 Participants	61.76 Years STANDARD_DEVIATION 12.47 • n=7 Participants	58.25 Years STANDARD_DEVIATION 12.89 • n=5 Participants
Age, Customized < 65 years	110 Participants n=5 Participants	25 Participants n=7 Participants	135 Participants n=5 Participants
Age, Customized 65 - <75 years	34 Participants n=5 Participants	11 Participants n=7 Participants	45 Participants n=5 Participants
Age, Customized 75 - <85 years	15 Participants n=5 Participants	3 Participants n=7 Participants	18 Participants n=5 Participants
Age, Customized >=85 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	24 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	17 Participants n=7 Participants	68 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	131 Participants n=5 Participants	39 Participants n=7 Participants	170 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	0 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	15 Participants n=5 Participants	0 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	117 Participants n=5 Participants	37 Participants n=7 Participants	154 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	18 Participants n=5 Participants	1 Participants n=7 Participants	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to approximately 24 months

Population: The analysis set included all enrolled participants who received at least 1 dose of study treatment. Participants were classified according to the cohort assigned at enrollment.

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=159 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) n=41 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Percentage of Participants With Confirmed Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)	27.7 Percentage of participants Interval 20.9 to 35.3	7.3 Percentage of participants Interval 1.5 to 19.9

SECONDARY outcome

Timeframe: From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately

Population: The safety analysis set included all enrolled participants who received at least 1 dose of study treatment.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device. TEAEs were those events with onset dates occurring during the on-treatment period. A Serious Adverse Event (SAE) was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=159 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) n=41 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) TEAEs	156 Participants	40 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) treatment-related TEAEs	148 Participants	34 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) grade >=3 TEAEs	114 Participants	22 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) grade >=3 treatment-related TEAEs	85 Participants	17 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) SAEs	50 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) treatment-related SAEs	12 Participants	4 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) TEAEs leading to discontinuation of all study drugs	5 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) treatment-related TEAEs leading to discontinuation of all study drugs	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) TEAEs leading to death	14 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) treatment-related TEAEs leading to death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately

Population: The safety analysis set included all enrolled participants who received at least 1 dose of study treatment. The number analyzed for each parameter in each treatment group was the number of participants evaluable for each parameter. Number of participants analyzed = participants evaluable for this outcome measure (OM), number analyzed = participants evaluable for the specific lab parameter per CTCAE criteria.

The laboratory results were graded according to the CTCAE v4.03 severity grade whenever applicable. Laboratory test abnormalities were summarized according to worst toxicity grade observed for each laboratory test. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day).

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=159 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) n=41 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: activated partial thromboplastin time prolonged)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: activated partial thromboplastin time prolonged)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: activated partial thromboplastin time prolonged)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: activated partial thromboplastin time prolonged)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: anemia)	27 Participants	9 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: anemia)	33 Participants	6 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: anemia)	61 Participants	12 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: anemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hemoglobin increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hemoglobin increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hemoglobin increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hemoglobin increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: International Normalized Ratio [INR] increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: INR increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: INR increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: INR increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: lymphocyte count decreased)	15 Participants	6 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: lymphocyte count decreased)	58 Participants	15 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: lymphocyte count decreased)	34 Participants	7 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: lymphocyte count decreased)	3 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: lymphocyte count increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: lymphocyte count increased)	3 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: lymphocyte count increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: lymphocyte count increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: neutrophil count decreased)	15 Participants	2 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: neutrophil count decreased)	42 Participants	8 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: neutrophil count decreased)	16 Participants	4 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: neutrophil count decreased)	3 Participants	1 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: platelet count decreased)	59 Participants	16 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: platelet count decreased)	16 Participants	3 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: platelet count decreased)	14 Participants	4 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: platelet count decreased)	11 Participants	1 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: white blood cell decreased)	45 Participants	14 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: white blood cell decreased)	52 Participants	11 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: white blood cell decreased)	15 Participants	5 Participants
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: white blood cell decreased)	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=159 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) n=41 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: alkaline phosphatase increased)	25 Participants	12 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: alanine aminotransferase increased)	30 Participants	10 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: alanine aminotransferase increased)	6 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: alanine aminotransferase increased)	3 Participants	3 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: alanine aminotransferase increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: alkaline phosphatase increased)	21 Participants	5 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: alkaline phosphatase increased)	7 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: alkaline phosphatase increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: aspartate aminotransferase increased)	35 Participants	5 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: aspartate aminotransferase increased)	13 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: aspartate aminotransferase increased)	2 Participants	4 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: aspartate aminotransferase increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: blood bilirubin increased)	7 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: blood bilirubin increased)	7 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: blood bilirubin increased)	2 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: blood bilirubin increased)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: creatine phosphokinase [CPK] increased)	22 Participants	3 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: CPK increased)	8 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: CPK increased)	2 Participants	3 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: CPK increased)	0 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: creatinine increased)	87 Participants	24 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: creatinine increased)	12 Participants	4 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: creatinine increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: creatinine increased)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: gamma glutamyl transferase [GGT] increased)	23 Participants	8 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: GGT increased)	16 Participants	5 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: GGT increased)	26 Participants	7 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: GGT increased)	1 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypercalcemia)	11 Participants	4 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypercalcemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypercalcemia)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypercalcemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hyperglycemia)	23 Participants	5 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hyperglycemia)	2 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hyperglycemia)	3 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hyperglycemia)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hyperkalemia)	13 Participants	3 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hyperkalemia)	6 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hyperkalemia)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hyperkalemia)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypermagnesemia)	9 Participants	4 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypermagnesemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypermagnesemia)	3 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypermagnesemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypernatremia)	8 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypernatremia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypernatremia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypernatremia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypoalbuminemia)	21 Participants	6 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypoalbuminemia)	10 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypoalbuminemia)	2 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypoalbuminemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypocalcemia)	27 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypocalcemia)	6 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypocalcemia)	3 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypocalcemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypoglycemia)	10 Participants	4 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypoglycemia)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypoglycemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypoglycemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypokalemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypokalemia)	24 Participants	8 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypokalemia)	4 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypokalemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypomagnesemia)	24 Participants	5 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypomagnesemia)	2 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypomagnesemia)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypomagnesemia)	1 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hyponatremia)	29 Participants	10 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hyponatremia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hyponatremia)	11 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hyponatremia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: hypophosphatemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: hypophosphatemia)	18 Participants	4 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: hypophosphatemia)	2 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: hypophosphatemia)	0 Participants	0 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: lipase increased)	13 Participants	4 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: lipase increased)	9 Participants	3 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: lipase increased)	7 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: lipase increased)	2 Participants	1 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 1 (Parameter: serum amylase increased)	16 Participants	3 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 2 (Parameter: serum amylase increased)	1 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 3 (Parameter: serum amylase increased)	2 Participants	2 Participants
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period New or worsened to grade 4 (Parameter: serum amylase increased)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1

Population: The avelumab PK concentration analysis set included all participants (Cohort 1 and Cohort 2 combined) who received at least 1 dose of study intervention and had at least one concentration measurement for avelumab. Number of participants analyzed = number of participants evaluable for this OM. Number analyzed = participants evaluable at the specific time point.

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=199 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab CYCLE1DAY1	NA microgram(mcg)/milliliter(mL) Geometric Coefficient of Variation NA Summary statistics were not presented for NALQ = 0.	—
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab CYCLE1DAY15	21.06 microgram(mcg)/milliliter(mL) Geometric Coefficient of Variation 58	—
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab CYCLE3DAY1	32.65 microgram(mcg)/milliliter(mL) Geometric Coefficient of Variation 63	—
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab CYCLE6DAY1	36.23 microgram(mcg)/milliliter(mL) Geometric Coefficient of Variation 60	—
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab CYCLE12DAY1	41.80 microgram(mcg)/milliliter(mL) Geometric Coefficient of Variation 60	—
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab CYCLE18DAY1	35.19 microgram(mcg)/milliliter(mL) Geometric Coefficient of Variation 54	—
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab CYCLE24DAY1	37.21 microgram(mcg)/milliliter(mL) Geometric Coefficient of Variation 54	—

SECONDARY outcome

Timeframe: One hour post-dose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1

Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=199 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Serum Maximum Concentration (Cmax) for Avelumab CYCLE1DAY1	223.0 mcg/mL Geometric Coefficient of Variation 39	—
Serum Maximum Concentration (Cmax) for Avelumab CYCLE1DAY15	221.6 mcg/mL Geometric Coefficient of Variation 38	—
Serum Maximum Concentration (Cmax) for Avelumab CYCLE3DAY1	225.6 mcg/mL Geometric Coefficient of Variation 34	—
Serum Maximum Concentration (Cmax) for Avelumab CYCLE6DAY1	222.3 mcg/mL Geometric Coefficient of Variation 37	—
Serum Maximum Concentration (Cmax) for Avelumab CYCLE12DAY1	248.2 mcg/mL Geometric Coefficient of Variation 25	—
Serum Maximum Concentration (Cmax) for Avelumab CYCLE18DAY1	265.9 mcg/mL Geometric Coefficient of Variation 20	—
Serum Maximum Concentration (Cmax) for Avelumab CYCLE24DAY1	286.1 mcg/mL Geometric Coefficient of Variation 21	—

SECONDARY outcome

Timeframe: Predose on Cycle 1 Days 1, 15 and Cycle 3 Day 1

Population: The talazoparib PK concentration analysis set included all participants (Cohort 1 and Cohort 2 combined) who received at least 1 dose of study intervention and had at least one Ctrough concentration measurement for talazoparib. Number of participants analyzed = number of participants evaluable for this OM. Number analyzed = participants evaluable at the specific time point.

Ctrough was defined as predose concentration during multiple dosing. The determination method of Ctrough was observing directly from data. The lower limit of quantification (LLQ) was 25 pg/mL. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented. Evaluable participants were participants with non-missing Ctrough concentrations at each specific time point and meeting 2 conditions: participants received 14 consecutive days of talazoparib dose without dosing interruption prior to sample collection (except on Cycle 1 Day 1) and sample collection within 24 hours ± 10% (2 hours and 24 minutes) after the previous day's dose and no more than 5 minutes (0.083 hours) after the administration of the dose on the day of PK sample collection. Predose PK samples on Cycle 1 Day 1 must have been collected prior to dose.

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=199 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Plasma Ctrough for Talazoparib CYCLE1DAY1 (Starting Dose: 1 mg QD)	NA picogram(pg)/mL Geometric Coefficient of Variation NA Summary statistics were not presented for NALQ = 0.	—
Plasma Ctrough for Talazoparib CYCLE1DAY15 (Starting Dose: 1 mg QD)	4649 picogram(pg)/mL Geometric Coefficient of Variation 61	—
Plasma Ctrough for Talazoparib CYCLE3DAY1 (Starting Dose: 1 mg QD)	3313 picogram(pg)/mL Geometric Coefficient of Variation 113	—
Plasma Ctrough for Talazoparib CYCLE1DAY1 (Starting Dose: 0.75 mg QD)	NA picogram(pg)/mL Geometric Coefficient of Variation NA Summary statistics were not presented for NALQ = 0.	—
Plasma Ctrough for Talazoparib CYCLE1DAY15 (Starting Dose: 0.75 mg QD)	7612 picogram(pg)/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation was not estimable due to insufficient number of participants with results.	—
Plasma Ctrough for Talazoparib CYCLE3DAY1 (Starting Dose: 0.75 mg QD)	4314 picogram(pg)/mL Geometric Coefficient of Variation 42	—

SECONDARY outcome

Timeframe: Postdose (samples collected within 2 hours post dose plus/minus 12 minutes) on Days 1,15 of Cycle 1, and Day 1 of Cycle 3

Population: The Analysis Population included all participants (Cohort 1 and Cohort 2 combined) who received at least 1 dose of talazoparib, had at least one non-missing concentration measurement at any collection scheduled time point, received 14 consecutive days of talazoparib dose without dosing interruption prior to sample collection (except on Cycle 1 Day 1) and sample collection was performed within ± 10% (12 minutes) of nominal time post-dose.

In this OM, the post-dose concentrations for talazoparib in plasma were reported.

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=106 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Plasma Post-dose Concentrations for Talazoparib CYCLE1DAY1 (Starting Dose: 1 mg QD)	1833 pg/mL Geometric Coefficient of Variation 275	—
Plasma Post-dose Concentrations for Talazoparib CYCLE1DAY15 (Starting Dose: 1 mg QD)	7985 pg/mL Geometric Coefficient of Variation 79	—
Plasma Post-dose Concentrations for Talazoparib CYCLE3DAY1 (Starting Dose: 1 mg QD)	7800 pg/mL Geometric Coefficient of Variation 69	—
Plasma Post-dose Concentrations for Talazoparib CYCLE1DAY1 (Starting Dose: 0.75 mg QD)	1663 pg/mL Geometric Coefficient of Variation 100	—
Plasma Post-dose Concentrations for Talazoparib CYCLE1DAY15 (Starting Dose: 0.75 mg QD)	12590 pg/mL Geometric Coefficient of Variation 47	—
Plasma Post-dose Concentrations for Talazoparib CYCLE3DAY1 (Starting Dose: 0.75 mg QD)	8366 pg/mL Geometric Coefficient of Variation 53	—

SECONDARY outcome

Timeframe: Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1

Population: Number of Participants Analyzed = participants in the immunogenicity analysis set who had at least 1 ADA sample collected for avelumab. Number Analyzed (N0) = participants with at least one valid ADA result at any time point; (N1) = participants with valid baseline ADA result; (N2) = participants with valid baseline ADA results and at least one valid post-baseline ADA result; (N3) = participants with at least one valid post-baseline ADA result and without positive baseline ADA result.

Blood samples were assayed for ADA using a validated assay. ADA never-positive = no positive ADA results at any time point. ADA ever-positive =at least one positive ADA result at any time point. Baseline ADA positive =a positive ADA result at baseline. Treatment-boosted ADA =a positive ADA result at baseline and the titer \>=8×baseline titer at least once after treatment with avelumab. Treatment-induced ADA = participant was ADA-negative at baseline and had at least one positive post-baseline ADA result; or the participant had at least one positive post-baseline ADA result if no baseline sample. Transient ADA response = participants with treatment-induced ADA had (a single positive ADA result or duration between first and last positive result \<16 weeks) and ADA result at the last assessment was not positive. Persistent ADA response =participants with treatment-induced ADA had duration between first and last positive ADA result \>=16 weeks or a positive ADA result at the last assessment.

Outcome measures

Outcome measures
Measure	Cohort 1 (BRCA 1/2 Defect) n=159 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.	Cohort 2 (ATM Defect) n=40 Participants Participants with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for participants with normal renal function or mild renal impairment until End of Treatment. Participants with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories ADA never-positive (n/N0)	153 Participants	39 Participants
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories ADA ever-positive (n/N0)	6 Participants	1 Participants
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories Baseline ADA positive (n/N1)	5 Participants	1 Participants
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories Treatment-boosted ADA (n/N2)	0 Participants	0 Participants
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories Treatment-induced ADA (n/N3)	1 Participants	0 Participants
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories Transient ADA response (n/N3)	1 Participants	0 Participants
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories Persistent ADA response (n/N3)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1

Population: The immunogenicity analysis set included participants who had at least 1 Nab sample collected for avelumab. Nabs data were not collected due to insufficient number of participants with persistent treatment-induced ADA response. Therefore, the number of participants analyzed for this OM was 0.

Nab ever-positive was defined as at least one positive Nab result at any time point. Samples positive for ADA with persistent treatment-induced ADA response could be analyzed for Nab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months

Population: All efficacy analyses were performed based on the full analysis set. The full analysis set included all enrolled participants who received at least 1 dose of study treatment. Participants were classified according to the cohort assigned at enrollment.

For participants with solid tumors, except mCRPC, OR was defined as a CR or PR per RECIST v1.1, both confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. For participants with mCRPC, OR was defined as the percentage of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per PCWG3 criteria. Per RECIST v1.1, CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Non-target PR lesions must be non-PD, where PD was unequivocal progression of pre-existing lesions.