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

• ClinicalTrials.gov Identifier: NCT03565991
• Recruitment Status: Terminated
• First Posted: June 21, 2018
• Results First Posted: August 7, 2023
• Last Update Posted: September 25, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Locally Advanced or Metastatic Solid Tumors; Genes, BRCA 1
• Interventions: Drug: Avelumab; Drug: Talazoparib
• Enrollment: 202

Participant Flow

Recruitment Details
Pre-assignment Details	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).

Arm/Group Title	Cohort 1 (BReast CAncer Gene [BRCA] 1/2 Defect)	Cohort 2 (Ataxia Telangiectasia Mutated [ATM] Defect)
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	159	41
Completed	1	0
Not Completed	158	41
Reason Not Completed
Other	11	0
Global deterioration of health status	14	4
Withdrawal by Subject	2	6
Progressive disease	121	29
Death	3	0
Adverse Event	7	2

Baseline Characteristics

Arm/Group Title		Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		159	41	200
Baseline Analysis Population Description		Baseline analysis population included all enrolled participants who received at least 1 dose of study treatment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	159 participants	41 participants	200 participants
		57.35 (12.88)	61.76 (12.47)	58.25 (12.89)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	159 participants	41 participants	200 participants
< 65 years		110 69.2%	25 61.0%	135 67.5%
65 - <75 years		34 21.4%	11 26.8%	45 22.5%
75 - <85 years		15 9.4%	3 7.3%	18 9.0%
>=85 years		0 0.0%	2 4.9%	2 1.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	159 participants	41 participants	200 participants
	Female	108 67.9%	24 58.5%	132 66.0%
	Male	51 32.1%	17 41.5%	68 34.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	159 participants	41 participants	200 participants
	Hispanic or Latino	11 6.9%	2 4.9%	13 6.5%
	Not Hispanic or Latino	131 82.4%	39 95.1%	170 85.0%
	Unknown or Not Reported	17 10.7%	0 0.0%	17 8.5%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	159 participants	41 participants	200 participants
Black or African American		8 5.0%	3 7.3%	11 5.5%
American Indian or Alaska Native		1 0.6%	0 0.0%	1 0.5%
Asian		15 9.4%	0 0.0%	15 7.5%
White		117 73.6%	37 90.2%	154 77.0%
Not reported		18 11.3%	1 2.4%	19 9.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Confirmed Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	27.7; (20.9 to 35.3)	7.3; (1.5 to 19.9)

2. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Measure Type: Count of Participants; Unit of Measure: Participants
TEAEs	156 98.1%	40 97.6%
treatment-related TEAEs	148 93.1%	34 82.9%
grade >=3 TEAEs	114 71.7%	22 53.7%
grade >=3 treatment-related TEAEs	85 53.5%	17 41.5%
SAEs	50 31.4%	7 17.1%
treatment-related SAEs	12 7.5%	4 9.8%
TEAEs leading to discontinuation of all study drugs	5 3.1%	2 4.9%
treatment-related TEAEs leading to discontinuation of all study drugs	0 0.0%	1 2.4%
TEAEs leading to death	14 8.8%	2 4.9%
treatment-related TEAEs leading to death	0 0.0%	0 0.0%

3. Secondary Outcome

Title	Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period
Description	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).
Time Frame	From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:		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.	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 Number of Participants Analyzed		159	41
Measure Type: Count of Participants; Unit of Measure: Participants
New or worsened to grade 1 (Parameter: activated partial thromboplastin time prolonged)	Number Analyzed	5 participants	1 participants
		0 0.0%	0 0.0%
New or worsened to grade 2 (Parameter: activated partial thromboplastin time prolonged)	Number Analyzed	5 participants	1 participants
		0 0.0%	0 0.0%
New or worsened to grade 3 (Parameter: activated partial thromboplastin time prolonged)	Number Analyzed	5 participants	1 participants
		0 0.0%	0 0.0%
New or worsened to grade 4 (Parameter: activated partial thromboplastin time prolonged)	Number Analyzed	5 participants	1 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: anemia)	Number Analyzed	151 participants	40 participants
		27 17.9%	9 22.5%
New or worsened to grade 2 (Parameter: anemia)	Number Analyzed	151 participants	40 participants
		33 21.9%	6 15.0%
New or worsened to grade 3 (Parameter: anemia)	Number Analyzed	151 participants	40 participants
		61 40.4%	12 30.0%
New or worsened to grade 4 (Parameter: anemia)	Number Analyzed	151 participants	40 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hemoglobin increased)	Number Analyzed	157 participants	41 participants
		1 0.6%	0 0.0%
New or worsened to grade 2 (Parameter: hemoglobin increased)	Number Analyzed	157 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 3 (Parameter: hemoglobin increased)	Number Analyzed	157 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 4 (Parameter: hemoglobin increased)	Number Analyzed	157 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: International Normalized Ratio [INR] increased)	Number Analyzed	6 participants	0 participants
		1 16.7%	0
New or worsened to grade 2 (Parameter: INR increased)	Number Analyzed	6 participants	0 participants
		0 0.0%	0
New or worsened to grade 3 (Parameter: INR increased)	Number Analyzed	6 participants	0 participants
		0 0.0%	0
New or worsened to grade 4 (Parameter: INR increased)	Number Analyzed	6 participants	0 participants
		0 0.0%	0
New or worsened to grade 1 (Parameter: lymphocyte count decreased)	Number Analyzed	154 participants	40 participants
		15 9.7%	6 15.0%
New or worsened to grade 2 (Parameter: lymphocyte count decreased)	Number Analyzed	154 participants	40 participants
		58 37.7%	15 37.5%
New or worsened to grade 3 (Parameter: lymphocyte count decreased)	Number Analyzed	154 participants	40 participants
		34 22.1%	7 17.5%
New or worsened to grade 4 (Parameter: lymphocyte count decreased)	Number Analyzed	154 participants	40 participants
		3 1.9%	0 0.0%
New or worsened to grade 1 (Parameter: lymphocyte count increased)	Number Analyzed	156 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 2 (Parameter: lymphocyte count increased)	Number Analyzed	156 participants	41 participants
		3 1.9%	0 0.0%
New or worsened to grade 3 (Parameter: lymphocyte count increased)	Number Analyzed	156 participants	41 participants
		1 0.6%	0 0.0%
New or worsened to grade 4 (Parameter: lymphocyte count increased)	Number Analyzed	156 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: neutrophil count decreased)	Number Analyzed	154 participants	40 participants
		15 9.7%	2 5.0%
New or worsened to grade 2 (Parameter: neutrophil count decreased)	Number Analyzed	154 participants	40 participants
		42 27.3%	8 20.0%
New or worsened to grade 3 (Parameter: neutrophil count decreased)	Number Analyzed	154 participants	40 participants
		16 10.4%	4 10.0%
New or worsened to grade 4 (Parameter: neutrophil count decreased)	Number Analyzed	154 participants	40 participants
		3 1.9%	1 2.5%
New or worsened to grade 1 (Parameter: platelet count decreased)	Number Analyzed	152 participants	41 participants
		59 38.8%	16 39.0%
New or worsened to grade 2 (Parameter: platelet count decreased)	Number Analyzed	152 participants	41 participants
		16 10.5%	3 7.3%
New or worsened to grade 3 (Parameter: platelet count decreased)	Number Analyzed	152 participants	41 participants
		14 9.2%	4 9.8%
New or worsened to grade 4 (Parameter: platelet count decreased)	Number Analyzed	152 participants	41 participants
		11 7.2%	1 2.4%
New or worsened to grade 1 (Parameter: white blood cell decreased)	Number Analyzed	156 participants	41 participants
		45 28.8%	14 34.1%
New or worsened to grade 2 (Parameter: white blood cell decreased)	Number Analyzed	156 participants	41 participants
		52 33.3%	11 26.8%
New or worsened to grade 3 (Parameter: white blood cell decreased)	Number Analyzed	156 participants	41 participants
		15 9.6%	5 12.2%
New or worsened to grade 4 (Parameter: white blood cell decreased)	Number Analyzed	156 participants	41 participants
		2 1.3%	0 0.0%

4. Secondary Outcome

Title	Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period
Description	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).
Time Frame	From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:		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.	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 Number of Participants Analyzed		159	41
Measure Type: Count of Participants; Unit of Measure: Participants
New or worsened to grade 1 (Parameter: alanine aminotransferase increased)	Number Analyzed	152 participants	41 participants
		30 19.7%	10 24.4%
New or worsened to grade 2 (Parameter: alanine aminotransferase increased)	Number Analyzed	152 participants	41 participants
		6 3.9%	0 0.0%
New or worsened to grade 3 (Parameter: alanine aminotransferase increased)	Number Analyzed	152 participants	41 participants
		3 2.0%	3 7.3%
New or worsened to grade 4 (Parameter: alanine aminotransferase increased)	Number Analyzed	152 participants	41 participants
		1 0.7%	0 0.0%
New or worsened to grade 1 (Parameter: alkaline phosphatase increased)	Number Analyzed	153 participants	41 participants
		25 16.3%	12 29.3%
New or worsened to grade 2 (Parameter: alkaline phosphatase increased)	Number Analyzed	153 participants	41 participants
		21 13.7%	5 12.2%
New or worsened to grade 3 (Parameter: alkaline phosphatase increased)	Number Analyzed	153 participants	41 participants
		7 4.6%	1 2.4%
New or worsened to grade 4 (Parameter: alkaline phosphatase increased)	Number Analyzed	153 participants	41 participants
		1 0.7%	0 0.0%
New or worsened to grade 1 (Parameter: aspartate aminotransferase increased)	Number Analyzed	150 participants	40 participants
		35 23.3%	5 12.5%
New or worsened to grade 2 (Parameter: aspartate aminotransferase increased)	Number Analyzed	150 participants	40 participants
		13 8.7%	2 5.0%
New or worsened to grade 3 (Parameter: aspartate aminotransferase increased)	Number Analyzed	150 participants	40 participants
		2 1.3%	4 10.0%
New or worsened to grade 4 (Parameter: aspartate aminotransferase increased)	Number Analyzed	150 participants	40 participants
		1 0.7%	0 0.0%
New or worsened to grade 1 (Parameter: blood bilirubin increased)	Number Analyzed	154 participants	40 participants
		7 4.5%	2 5.0%
New or worsened to grade 2 (Parameter: blood bilirubin increased)	Number Analyzed	154 participants	40 participants
		7 4.5%	2 5.0%
New or worsened to grade 3 (Parameter: blood bilirubin increased)	Number Analyzed	154 participants	40 participants
		2 1.3%	1 2.5%
New or worsened to grade 4 (Parameter: blood bilirubin increased)	Number Analyzed	154 participants	40 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: creatine phosphokinase [CPK] increased)	Number Analyzed	151 participants	41 participants
		22 14.6%	3 7.3%
New or worsened to grade 2 (Parameter: CPK increased)	Number Analyzed	151 participants	41 participants
		8 5.3%	1 2.4%
New or worsened to grade 3 (Parameter: CPK increased)	Number Analyzed	151 participants	41 participants
		2 1.3%	3 7.3%
New or worsened to grade 4 (Parameter: CPK increased)	Number Analyzed	151 participants	41 participants
		0 0.0%	1 2.4%
New or worsened to grade 1 (Parameter: creatinine increased)	Number Analyzed	153 participants	40 participants
		87 56.9%	24 60.0%
New or worsened to grade 2 (Parameter: creatinine increased)	Number Analyzed	153 participants	40 participants
		12 7.8%	4 10.0%
New or worsened to grade 3 (Parameter: creatinine increased)	Number Analyzed	153 participants	40 participants
		1 0.7%	0 0.0%
New or worsened to grade 4 (Parameter: creatinine increased)	Number Analyzed	153 participants	40 participants
		1 0.7%	0 0.0%
New or worsened to grade 1 (Parameter: gamma glutamyl transferase [GGT] increased)	Number Analyzed	147 participants	40 participants
		23 15.6%	8 20.0%
New or worsened to grade 2 (Parameter: GGT increased)	Number Analyzed	147 participants	40 participants
		16 10.9%	5 12.5%
New or worsened to grade 3 (Parameter: GGT increased)	Number Analyzed	147 participants	40 participants
		26 17.7%	7 17.5%
New or worsened to grade 4 (Parameter: GGT increased)	Number Analyzed	147 participants	40 participants
		1 0.7%	1 2.5%
New or worsened to grade 1 (Parameter: hypercalcemia)	Number Analyzed	156 participants	41 participants
		11 7.1%	4 9.8%
New or worsened to grade 2 (Parameter: hypercalcemia)	Number Analyzed	156 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 3 (Parameter: hypercalcemia)	Number Analyzed	156 participants	41 participants
		1 0.6%	0 0.0%
New or worsened to grade 4 (Parameter: hypercalcemia)	Number Analyzed	156 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hyperglycemia)	Number Analyzed	155 participants	41 participants
		23 14.8%	5 12.2%
New or worsened to grade 2 (Parameter: hyperglycemia)	Number Analyzed	155 participants	41 participants
		2 1.3%	0 0.0%
New or worsened to grade 3 (Parameter: hyperglycemia)	Number Analyzed	155 participants	41 participants
		3 1.9%	2 4.9%
New or worsened to grade 4 (Parameter: hyperglycemia)	Number Analyzed	155 participants	41 participants
		1 0.6%	0 0.0%
New or worsened to grade 1 (Parameter: hyperkalemia)	Number Analyzed	156 participants	40 participants
		13 8.3%	3 7.5%
New or worsened to grade 2 (Parameter: hyperkalemia)	Number Analyzed	156 participants	40 participants
		6 3.8%	0 0.0%
New or worsened to grade 3 (Parameter: hyperkalemia)	Number Analyzed	156 participants	40 participants
		1 0.6%	0 0.0%
New or worsened to grade 4 (Parameter: hyperkalemia)	Number Analyzed	156 participants	40 participants
		1 0.6%	0 0.0%
New or worsened to grade 1 (Parameter: hypermagnesemia)	Number Analyzed	155 participants	41 participants
		9 5.8%	4 9.8%
New or worsened to grade 2 (Parameter: hypermagnesemia)	Number Analyzed	155 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 3 (Parameter: hypermagnesemia)	Number Analyzed	155 participants	41 participants
		3 1.9%	0 0.0%
New or worsened to grade 4 (Parameter: hypermagnesemia)	Number Analyzed	155 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hypernatremia)	Number Analyzed	156 participants	41 participants
		8 5.1%	1 2.4%
New or worsened to grade 2 (Parameter: hypernatremia)	Number Analyzed	156 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 3 (Parameter: hypernatremia)	Number Analyzed	156 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 4 (Parameter: hypernatremia)	Number Analyzed	156 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hypoalbuminemia)	Number Analyzed	150 participants	39 participants
		21 14.0%	6 15.4%
New or worsened to grade 2 (Parameter: hypoalbuminemia)	Number Analyzed	150 participants	39 participants
		10 6.7%	2 5.1%
New or worsened to grade 3 (Parameter: hypoalbuminemia)	Number Analyzed	150 participants	39 participants
		2 1.3%	1 2.6%
New or worsened to grade 4 (Parameter: hypoalbuminemia)	Number Analyzed	150 participants	39 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hypocalcemia)	Number Analyzed	153 participants	41 participants
		27 17.6%	2 4.9%
New or worsened to grade 2 (Parameter: hypocalcemia)	Number Analyzed	153 participants	41 participants
		6 3.9%	1 2.4%
New or worsened to grade 3 (Parameter: hypocalcemia)	Number Analyzed	153 participants	41 participants
		3 2.0%	0 0.0%
New or worsened to grade 4 (Parameter: hypocalcemia)	Number Analyzed	153 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hypoglycemia)	Number Analyzed	155 participants	41 participants
		10 6.5%	4 9.8%
New or worsened to grade 2 (Parameter: hypoglycemia)	Number Analyzed	155 participants	41 participants
		1 0.6%	0 0.0%
New or worsened to grade 3 (Parameter: hypoglycemia)	Number Analyzed	155 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 4 (Parameter: hypoglycemia)	Number Analyzed	155 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hypokalemia)	Number Analyzed	155 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 2 (Parameter: hypokalemia)	Number Analyzed	155 participants	41 participants
		24 15.5%	8 19.5%
New or worsened to grade 3 (Parameter: hypokalemia)	Number Analyzed	155 participants	41 participants
		4 2.6%	1 2.4%
New or worsened to grade 4 (Parameter: hypokalemia)	Number Analyzed	155 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hypomagnesemia)	Number Analyzed	156 participants	41 participants
		24 15.4%	5 12.2%
New or worsened to grade 2 (Parameter: hypomagnesemia)	Number Analyzed	156 participants	41 participants
		2 1.3%	0 0.0%
New or worsened to grade 3 (Parameter: hypomagnesemia)	Number Analyzed	156 participants	41 participants
		1 0.6%	0 0.0%
New or worsened to grade 4 (Parameter: hypomagnesemia)	Number Analyzed	156 participants	41 participants
		1 0.6%	0 0.0%
New or worsened to grade 1 (Parameter: hyponatremia)	Number Analyzed	153 participants	40 participants
		29 19.0%	10 25.0%
New or worsened to grade 2 (Parameter: hyponatremia)	Number Analyzed	153 participants	40 participants
		0 0.0%	0 0.0%
New or worsened to grade 3 (Parameter: hyponatremia)	Number Analyzed	153 participants	40 participants
		11 7.2%	2 5.0%
New or worsened to grade 4 (Parameter: hyponatremia)	Number Analyzed	153 participants	40 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: hypophosphatemia)	Number Analyzed	153 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 2 (Parameter: hypophosphatemia)	Number Analyzed	153 participants	41 participants
		18 11.8%	4 9.8%
New or worsened to grade 3 (Parameter: hypophosphatemia)	Number Analyzed	153 participants	41 participants
		2 1.3%	1 2.4%
New or worsened to grade 4 (Parameter: hypophosphatemia)	Number Analyzed	153 participants	41 participants
		0 0.0%	0 0.0%
New or worsened to grade 1 (Parameter: lipase increased)	Number Analyzed	157 participants	41 participants
		13 8.3%	4 9.8%
New or worsened to grade 2 (Parameter: lipase increased)	Number Analyzed	157 participants	41 participants
		9 5.7%	3 7.3%
New or worsened to grade 3 (Parameter: lipase increased)	Number Analyzed	157 participants	41 participants
		7 4.5%	2 4.9%
New or worsened to grade 4 (Parameter: lipase increased)	Number Analyzed	157 participants	41 participants
		2 1.3%	1 2.4%
New or worsened to grade 1 (Parameter: serum amylase increased)	Number Analyzed	156 participants	41 participants
		16 10.3%	3 7.3%
New or worsened to grade 2 (Parameter: serum amylase increased)	Number Analyzed	156 participants	41 participants
		1 0.6%	2 4.9%
New or worsened to grade 3 (Parameter: serum amylase increased)	Number Analyzed	156 participants	41 participants
		2 1.3%	2 4.9%
New or worsened to grade 4 (Parameter: serum amylase increased)	Number Analyzed	156 participants	41 participants
		1 0.6%	1 2.4%

5. Secondary Outcome

Title	Serum Lowest (Trough) Concentration (Ctrough) of Avelumab
Description	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 0.2 mcg/mL. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented.
Time Frame	Predose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Avelumab 800 mg Intravenous (IV) Q2W Plus Talazoparib
Arm/Group Description:		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 Number of Participants Analyzed		199
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: microgram(mcg)/milliliter(mL)
CYCLE1DAY1	Number Analyzed	180 participants
		NA [1]; (NA%)
CYCLE1DAY15	Number Analyzed	164 participants
		21.06; (58%)
CYCLE3DAY1	Number Analyzed	110 participants
		32.65; (63%)
CYCLE6DAY1	Number Analyzed	83 participants
		36.23; (60%)
CYCLE12DAY1	Number Analyzed	35 participants
		41.80; (60%)
CYCLE18DAY1	Number Analyzed	16 participants
		35.19; (54%)
CYCLE24DAY1	Number Analyzed	10 participants
		37.21; (54%)

[1]

Summary statistics were not presented for NALQ = 0.

6. Secondary Outcome

Title	Serum Maximum Concentration (Cmax) for Avelumab
Description	Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.
Time Frame	One hour post-dose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Avelumab 800 mg IV Q2W Plus Talazoparib
Arm/Group Description:		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 Number of Participants Analyzed		199
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg/mL
CYCLE1DAY1	Number Analyzed	161 participants
		223.0; (39%)
CYCLE1DAY15	Number Analyzed	146 participants
		221.6; (38%)
CYCLE3DAY1	Number Analyzed	114 participants
		225.6; (34%)
CYCLE6DAY1	Number Analyzed	79 participants
		222.3; (37%)
CYCLE12DAY1	Number Analyzed	35 participants
		248.2; (25%)
CYCLE18DAY1	Number Analyzed	17 participants
		265.9; (20%)
CYCLE24DAY1	Number Analyzed	9 participants
		286.1; (21%)

7. Secondary Outcome

Title	Plasma Ctrough for Talazoparib
Description	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.
Time Frame	Predose on Cycle 1 Days 1, 15 and Cycle 3 Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Avelumab 800 mg IV Q2W Plus Talazoparib
Arm/Group Description:		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 Number of Participants Analyzed		199
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: picogram(pg)/mL
CYCLE1DAY1 (Starting Dose: 1 mg QD)	Number Analyzed	170 participants
		NA [1]; (NA%)
CYCLE1DAY15 (Starting Dose: 1 mg QD)	Number Analyzed	62 participants
		4649; (61%)
CYCLE3DAY1 (Starting Dose: 1 mg QD)	Number Analyzed	30 participants
		3313; (113%)
CYCLE1DAY1 (Starting Dose: 0.75 mg QD)	Number Analyzed	16 participants
		NA [1]; (NA%)
CYCLE1DAY15 (Starting Dose: 0.75 mg QD)	Number Analyzed	2 participants
		7612 [2]; (NA%)
CYCLE3DAY1 (Starting Dose: 0.75 mg QD)	Number Analyzed	4 participants
		4314; (42%)

[1]

Summary statistics were not presented for NALQ = 0.

[2]

Geometric Coefficient of Variation was not estimable due to insufficient number of participants with results.

8. Secondary Outcome

Title	Plasma Post-dose Concentrations for Talazoparib
Description	In this OM, the post-dose concentrations for talazoparib in plasma were reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Avelumab 800 mg IV Q2W Plus Talazoparib
Arm/Group Description:		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 Number of Participants Analyzed		106
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: pg/mL
CYCLE1DAY1 (Starting Dose: 1 mg QD)	Number Analyzed	76 participants
		1833; (275%)
CYCLE1DAY15 (Starting Dose: 1 mg QD)	Number Analyzed	51 participants
		7985; (79%)
CYCLE3DAY1 (Starting Dose: 1 mg QD)	Number Analyzed	22 participants
		7800; (69%)
CYCLE1DAY1 (Starting Dose: 0.75 mg QD)	Number Analyzed	6 participants
		1663; (100%)
CYCLE1DAY15 (Starting Dose: 0.75 mg QD)	Number Analyzed	6 participants
		12590; (47%)
CYCLE3DAY1 (Starting Dose: 0.75 mg QD)	Number Analyzed	3 participants
		8366; (53%)

9. Secondary Outcome

Title	Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:		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.	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 Number of Participants Analyzed		159	40
Measure Type: Count of Participants; Unit of Measure: Participants
ADA never-positive (n/N0)	Number Analyzed	159 participants	40 participants
		153 96.2%	39 97.5%
ADA ever-positive (n/N0)	Number Analyzed	159 participants	40 participants
		6 3.8%	1 2.5%
Baseline ADA positive (n/N1)	Number Analyzed	150 participants	38 participants
		5 3.3%	1 2.6%
Treatment-boosted ADA (n/N2)	Number Analyzed	143 participants	37 participants
		0 0.0%	0 0.0%
Treatment-induced ADA (n/N3)	Number Analyzed	147 participants	38 participants
		1 0.7%	0 0.0%
Transient ADA response (n/N3)	Number Analyzed	147 participants	38 participants
		1 0.7%	0 0.0%
Persistent ADA response (n/N3)	Number Analyzed	147 participants	38 participants
		0 0.0%	0 0.0%

10. Secondary Outcome

Title	Number of Participants With Neutralizing Antibodies (Nab) Levels Against Avelumab Ever-Positive
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

11. Secondary Outcome

Title	Percentage of Participants With Confirmed OR as Assessed by The Investigator
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	34.6; (27.2 to 42.5)	14.6; (5.6 to 29.2)

12. Secondary Outcome

Title	Time to Tumor Response (TTR) as Assessed by BICR
Description	For participants with solid tumors, except mCRPC: TTR was defined for participants with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a Best Overall Response (BOR) of CR or PR per RECIST v1.1.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all enrolled participants who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by BICR.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	44	3
Median (Full Range); Unit of Measure: Months
	1.82; (1.5 to 12.1)	5.52; (1.6 to 16.8)

13. Secondary Outcome

Title	TTR as Assessed by Investigator
Description	For participants with solid tumors, except mCRPC: TTR was defined for participants with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a BOR of CR or PR per RECIST v1.1.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all enrolled participants who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by investigator.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	55	6
Median (Full Range); Unit of Measure: Months
	1.84; (1.5 to 18.4)	3.99; (1.9 to 14.0)

14. Secondary Outcome

Title	Duration of Response (DoR) as Assessed by BICR
Description	For participants with solid tumors, except mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occured first. For participants with mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occured first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all enrolled participants who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by BICR.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	44	3
Median (95% Confidence Interval); Unit of Measure: Months
	12.5 [1]; (7.5 to NA)	NA [2]; (6.7 to NA)

[1]

The reason for NA is that the upper limit of the confidence interval is not crossing the 50% bound.

[2]

The reason for NA is that the median and upper limit of the confidence interval are not crossing the 50% bound.

15. Secondary Outcome

Title	DoR as Assessed by Investigator
Description	For participants with solid tumors, except mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. For participants with mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all enrolled participants who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by investigator.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	55	6
Median (95% Confidence Interval); Unit of Measure: Months
	8.8; (7.5 to 10.7)	7.1; (5.5 to 9.7)

16. Secondary Outcome

Title	Progression Free Survival (PFS) as Assessed by BICR
Description	For participants with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Median (95% Confidence Interval); Unit of Measure: Months
	3.7; (3.1 to 5.4)	3.5; (1.8 to 5.5)

17. Secondary Outcome

Title	PFS as Assessed by Investigator
Description	For participants with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Median (95% Confidence Interval); Unit of Measure: Months
	5.3; (3.7 to 5.6)	3.7; (2.1 to 7.4)

18. Secondary Outcome

Title	Overall Survival (OS) for All Participants
Description	OS was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Median (95% Confidence Interval); Unit of Measure: Months
	11.9; (10.1 to 13.7)	16.4; (12.8 to 21.9)

19. Secondary Outcome

Title	Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC
Description	For participants with mCRPC, time to PSA progression was defined as the time from the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained >=3 weeks (21 days) later.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all participants with mCRPC who received at least 1 dose of study intervention.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	26	5
Median (95% Confidence Interval); Unit of Measure: Months
	6.5; (3.7 to 12.7)	11.3 [1]; (3.7 to NA)

[1]

The upper limit of the confidence interval is not crossing the 50% bound.

20. Secondary Outcome

Title	Number of Participants With Confirmed PSA Response
Description	For participants with mCRPC, PSA response was defined as confirmed PSA decline >=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must have been confirmed by a second consecutive value at least 3 weeks later.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all participants with mCRPC who received at least 1 dose of study intervention.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	26	5
Measure Type: Count of Participants; Unit of Measure: Participants
	17 65.4%	2 40.0%

21. Secondary Outcome

Title	Number of Participants With Circulating Tumor Cell (CTC) Count Conversion
Description	For participants with mCRPC, CTC count conversion was defined as a decrease in CTC count from >=5 CTC per 7.5 mL of blood at baseline to <5 CTC per 7.5 mL of blood anytime on study.
Time Frame	Day 1 of Cycle 1 to Cycle 4

Outcome Measure Data

Analysis Population Description

The analysis population included all enrolled participants with mCRPC who received at least 1 dose of study treatment, and with CTC count >=5 CTC per 7.5 mL of blood at baseline.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	13	2
Measure Type: Count of Participants; Unit of Measure: Participants
	11 84.6%	1 50.0%

22. Secondary Outcome

Title	Number of Participants With Cancer Antigen 125 (CA-125) Response
Description	For participants with ovarian cancer, CA-125 response was defined as at least a 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.
Time Frame	Baseline, Day 1 of each treatment Cycle, maximum up to 4.3 years approximately

Outcome Measure Data

Analysis Population Description

The analysis population included all participants with ovarian cancer who received at least 1 dose of study intervention.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	26	3
Measure Type: Count of Participants; Unit of Measure: Participants
	9 34.6%	0 0.0%

23. Secondary Outcome

Title	Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Expression in Baseline Tumor Tissue
Description	PD-L1 expression on tumor and infiltrating immune cells was measured by immunohistochemistry (IHC). PD-L1 expression level was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. This OM reported the number of participants classified as positive according to scoring algorithms and cut-offs established from external sources.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The biomarker analysis set included all participants who received at least 1 dose of study treatment and had at least 1 screening biomarker assessment.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Measure Type: Count of Participants; Unit of Measure: Participants
	27 17.0%	0 0.0%

24. Secondary Outcome

Title	Number of Participants With Different Status for Defects in BRCA1, BRCA2 and ATM
Description	Participants were enrolled in the two cohorts based on BRCA 1/2 and ATM defect status assessed by the local laboratory. The participant BRCA and ATM status was assessed retrospectively by central laboratory, that may differ from the status assessed by the local laboratory. The ATM participants with a negative ATM status per the central laboratory were reported to have a positive ATM status per the local laboratory. Therefore, participants with negative ATM status might have been included in the ATM defect cohort. For defects in BRCA1, BRCA2 and ATM by central laboratory analysis, participants were classified as positive, negative, not analyzable or missing. The number of participants in each category of BRCA 1 defect, BRCA 2 defect, BRCA 1 or BRCA 2 defect and ATM defect were presented.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The biomarker analysis set included all participants who received at least 1 dose of study treatment and had at least 1 screening biomarker assessment.

Arm/Group Title		Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:		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.	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 Number of Participants Analyzed		159	41
Measure Type: Count of Participants; Unit of Measure: Participants
BRCA1 status	Positive	52 32.7%	0 0.0%
	Negative	65 40.9%	29 70.7%
	Not analyzable	21 13.2%	4 9.8%
	Missing	21 13.2%	8 19.5%
BRCA2 status	Positive	53 33.3%	1 2.4%
	Negative	64 40.3%	28 68.3%
	Not analyzable	21 13.2%	4 9.8%
	Missing	21 13.2%	8 19.5%
BRCA status	Positive	105 66.0%	1 2.4%
	Negative	12 7.5%	28 68.3%
	Not analyzable	21 13.2%	4 9.8%
	Missing	21 13.2%	8 19.5%
ATM status	Positive	2 1.3%	26 63.4%
	Negative	115 72.3%	3 7.3%
	Not analyzable	21 13.2%	4 9.8%
	Missing	21 13.2%	8 19.5%

25. Secondary Outcome

Title	Number of Participants by Status of Tumor Mutational Burden (TMB) at Baseline
Description	TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. TMB categories were defined as high, low for a number of mutations per megabase >=10 and <10, respectively. The TMB category 'Not analyzable' included participants with available samples but not evaluable. The TMB category 'Missing' included participants with no sample available. The number of participants in each category at only baseline were tabulated.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The biomarker analysis set included all participants who received at least 1 dose of study treatment and had at least 1 screening biomarker assessment.

Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description:	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.	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 Number of Participants Analyzed	159	41
Measure Type: Count of Participants; Unit of Measure: Participants
TMB status high	9 5.7%	2 4.9%
TMB status low	95 59.7%	23 56.1%
TMB status not analyzable	34 21.4%	8 19.5%
TMB status missing	21 13.2%	8 19.5%

Adverse Events

Time Frame	From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately.
Adverse Event Reporting Description	The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Arm/Group Title	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
Arm/Group Description	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.	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.
All-Cause Mortality
	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	15/159 (9.43%)	3/41 (7.32%)
Serious Adverse Events
	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	50/159 (31.45%)	7/41 (17.07%)
Blood and lymphatic system disorders
Anaemia * 1	4/159 (2.52%)	2/41 (4.88%)
Bone marrow disorder * 1	1/159 (0.63%)	0/41 (0.00%)
Febrile neutropenia * 1	2/159 (1.26%)	0/41 (0.00%)
Neutropenia * 1	0/159 (0.00%)	1/41 (2.44%)
Thrombocytopenia * 1	1/159 (0.63%)	1/41 (2.44%)
Cardiac disorders
Atrioventricular block complete * 1	1/159 (0.63%)	0/41 (0.00%)
Atrioventricular block second degree * 1	2/159 (1.26%)	0/41 (0.00%)
Cardiac failure * 1	1/159 (0.63%)	0/41 (0.00%)
Pericardial effusion * 1	1/159 (0.63%)	0/41 (0.00%)
Eye disorders
Eye disorder * 1	1/159 (0.63%)	0/41 (0.00%)
Gastrointestinal disorders
Diarrhoea * 1	0/159 (0.00%)	1/41 (2.44%)
Gastritis * 1	1/159 (0.63%)	0/41 (0.00%)
Intestinal obstruction * 1	3/159 (1.89%)	0/41 (0.00%)
Nausea * 1	1/159 (0.63%)	0/41 (0.00%)
Obstruction gastric * 1	1/159 (0.63%)	0/41 (0.00%)
Small intestinal perforation * 1	1/159 (0.63%)	0/41 (0.00%)
Small intestine polyp * 1	0/159 (0.00%)	1/41 (2.44%)
Subileus * 1	1/159 (0.63%)	0/41 (0.00%)
Vomiting * 1	2/159 (1.26%)	0/41 (0.00%)
General disorders
Disease progression * 1	8/159 (5.03%)	2/41 (4.88%)
Pyrexia * 1	2/159 (1.26%)	1/41 (2.44%)
Hepatobiliary disorders
Cholecystitis * 1	1/159 (0.63%)	0/41 (0.00%)
Drug-induced liver injury * 1	0/159 (0.00%)	1/41 (2.44%)
Immune-mediated hepatitis * 1	1/159 (0.63%)	0/41 (0.00%)
Jaundice * 1	0/159 (0.00%)	1/41 (2.44%)
Liver injury * 1	0/159 (0.00%)	1/41 (2.44%)
Infections and infestations
Abdominal wall abscess * 1	0/159 (0.00%)	1/41 (2.44%)
Bacterial abdominal infection * 1	1/159 (0.63%)	0/41 (0.00%)
COVID-19 * 1	1/159 (0.63%)	0/41 (0.00%)
Clostridial infection * 1	1/159 (0.63%)	0/41 (0.00%)
Clostridium difficile colitis * 1	1/159 (0.63%)	0/41 (0.00%)
Pneumonia * 1	4/159 (2.52%)	1/41 (2.44%)
Sepsis * 1	3/159 (1.89%)	0/41 (0.00%)
Septic shock * 1	1/159 (0.63%)	0/41 (0.00%)
Urinary tract infection * 1	1/159 (0.63%)	1/41 (2.44%)
Urosepsis * 1	0/159 (0.00%)	1/41 (2.44%)
Injury, poisoning and procedural complications
Fracture * 1	1/159 (0.63%)	0/41 (0.00%)
Infusion related reaction * 1	1/159 (0.63%)	0/41 (0.00%)
Investigations
Alanine aminotransferase increased * 1	1/159 (0.63%)	2/41 (4.88%)
Aspartate aminotransferase increased * 1	1/159 (0.63%)	2/41 (4.88%)
Blood alkaline phosphatase increased * 1	1/159 (0.63%)	0/41 (0.00%)
Gamma-glutamyltransferase increased * 1	0/159 (0.00%)	1/41 (2.44%)
Liver function test increased * 1	0/159 (0.00%)	1/41 (2.44%)
Neutrophil count decreased * 1	1/159 (0.63%)	0/41 (0.00%)
Platelet count decreased * 1	1/159 (0.63%)	0/41 (0.00%)
Troponin T increased * 1	1/159 (0.63%)	0/41 (0.00%)
Weight decreased * 1	1/159 (0.63%)	0/41 (0.00%)
Musculoskeletal and connective tissue disorders
Myositis * 1	0/159 (0.00%)	1/41 (2.44%)
Osteitis * 1	1/159 (0.63%)	0/41 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain * 1	1/159 (0.63%)	0/41 (0.00%)
Malignant neoplasm progression * 1	1/159 (0.63%)	0/41 (0.00%)
Metastases to meninges * 1	1/159 (0.63%)	0/41 (0.00%)
Neoplasm progression * 1	1/159 (0.63%)	0/41 (0.00%)
Nervous system disorders
Depressed level of consciousness * 1	1/159 (0.63%)	0/41 (0.00%)
Migraine * 1	1/159 (0.63%)	0/41 (0.00%)
Seizure * 1	1/159 (0.63%)	0/41 (0.00%)
Syncope * 1	2/159 (1.26%)	0/41 (0.00%)
Psychiatric disorders
Confusional state * 1	1/159 (0.63%)	0/41 (0.00%)
Renal and urinary disorders
Acute kidney injury * 1	1/159 (0.63%)	1/41 (2.44%)
Hydronephrosis * 1	1/159 (0.63%)	0/41 (0.00%)
Nephrolithiasis * 1	0/159 (0.00%)	1/41 (2.44%)
Ureteric obstruction * 1	1/159 (0.63%)	0/41 (0.00%)
Ureterolithiasis * 1	0/159 (0.00%)	1/41 (2.44%)
Urethral obstruction * 1	1/159 (0.63%)	0/41 (0.00%)
Urinary tract obstruction * 1	1/159 (0.63%)	0/41 (0.00%)
Reproductive system and breast disorders
Pelvic pain * 1	1/159 (0.63%)	0/41 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	3/159 (1.89%)	0/41 (0.00%)
Pleural effusion * 1	1/159 (0.63%)	0/41 (0.00%)
Pneumothorax * 1	1/159 (0.63%)	0/41 (0.00%)
Pulmonary embolism * 1	3/159 (1.89%)	0/41 (0.00%)
Respiratory failure * 1	1/159 (0.63%)	0/41 (0.00%)
Vascular disorders
Hypotension * 1	1/159 (0.63%)	0/41 (0.00%)
1 Term from vocabulary, MedDRA v25.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort 1 (BRCA 1/2 Defect)	Cohort 2 (ATM Defect)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	153/159 (96.23%)	40/41 (97.56%)
Blood and lymphatic system disorders
Anaemia * 1	81/159 (50.94%)	18/41 (43.90%)
Neutropenia * 1	20/159 (12.58%)	4/41 (9.76%)
Thrombocytopenia * 1	27/159 (16.98%)	5/41 (12.20%)
Endocrine disorders
Hypothyroidism * 1	10/159 (6.29%)	5/41 (12.20%)
Gastrointestinal disorders
Abdominal distension * 1	5/159 (3.14%)	6/41 (14.63%)
Abdominal pain * 1	30/159 (18.87%)	6/41 (14.63%)
Ascites * 1	1/159 (0.63%)	3/41 (7.32%)
Constipation * 1	39/159 (24.53%)	8/41 (19.51%)
Diarrhoea * 1	36/159 (22.64%)	10/41 (24.39%)
Dyspepsia * 1	10/159 (6.29%)	3/41 (7.32%)
Nausea * 1	73/159 (45.91%)	21/41 (51.22%)
Vomiting * 1	39/159 (24.53%)	11/41 (26.83%)
General disorders
Asthenia * 1	27/159 (16.98%)	2/41 (4.88%)
Chills * 1	17/159 (10.69%)	5/41 (12.20%)
Fatigue * 1	50/159 (31.45%)	19/41 (46.34%)
Influenza like illness * 1	10/159 (6.29%)	2/41 (4.88%)
Oedema peripheral * 1	12/159 (7.55%)	4/41 (9.76%)
Pyrexia * 1	28/159 (17.61%)	3/41 (7.32%)
Infections and infestations
Sinusitis * 1	1/159 (0.63%)	3/41 (7.32%)
Upper respiratory tract infection * 1	12/159 (7.55%)	3/41 (7.32%)
Urinary tract infection * 1	11/159 (6.92%)	7/41 (17.07%)
Injury, poisoning and procedural complications
Infusion related reaction * 1	22/159 (13.84%)	3/41 (7.32%)
Investigations
Alanine aminotransferase increased * 1	16/159 (10.06%)	7/41 (17.07%)
Aspartate aminotransferase increased * 1	18/159 (11.32%)	6/41 (14.63%)
Blood bilirubin increased * 1	8/159 (5.03%)	3/41 (7.32%)
Blood creatine phosphokinase increased * 1	7/159 (4.40%)	4/41 (9.76%)
Blood creatinine increased * 1	3/159 (1.89%)	5/41 (12.20%)
Gamma-glutamyltransferase increased * 1	9/159 (5.66%)	3/41 (7.32%)
Lymphocyte count decreased * 1	2/159 (1.26%)	3/41 (7.32%)
Neutrophil count decreased * 1	21/159 (13.21%)	5/41 (12.20%)
Platelet count decreased * 1	25/159 (15.72%)	11/41 (26.83%)
Weight decreased * 1	10/159 (6.29%)	2/41 (4.88%)
White blood cell count decreased * 1	12/159 (7.55%)	4/41 (9.76%)
Metabolism and nutrition disorders
Decreased appetite * 1	33/159 (20.75%)	12/41 (29.27%)
Hypokalaemia * 1	8/159 (5.03%)	5/41 (12.20%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	30/159 (18.87%)	11/41 (26.83%)
Back pain * 1	21/159 (13.21%)	10/41 (24.39%)
Myalgia * 1	16/159 (10.06%)	2/41 (4.88%)
Neck pain * 1	9/159 (5.66%)	2/41 (4.88%)
Pain in extremity * 1	7/159 (4.40%)	5/41 (12.20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain * 1	2/159 (1.26%)	3/41 (7.32%)
Nervous system disorders
Dizziness * 1	19/159 (11.95%)	1/41 (2.44%)
Headache * 1	35/159 (22.01%)	6/41 (14.63%)
Peripheral sensory neuropathy * 1	5/159 (3.14%)	3/41 (7.32%)
Psychiatric disorders
Insomnia * 1	21/159 (13.21%)	5/41 (12.20%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	19/159 (11.95%)	5/41 (12.20%)
Dyspnoea * 1	34/159 (21.38%)	8/41 (19.51%)
Nasal congestion * 1	10/159 (6.29%)	1/41 (2.44%)
Productive cough * 1	8/159 (5.03%)	3/41 (7.32%)
Skin and subcutaneous tissue disorders
Alopecia * 1	19/159 (11.95%)	3/41 (7.32%)
Dry skin * 1	5/159 (3.14%)	4/41 (9.76%)
Pruritus * 1	10/159 (6.29%)	1/41 (2.44%)
Vascular disorders
Hot flush * 1	1/159 (0.63%)	3/41 (7.32%)
1 Term from vocabulary, MedDRA v25.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

• 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):

Schram AM, Colombo N, Arrowsmith E, Narayan V, Yonemori K, Scambia G, Zelnak A, Bauer TM, Jin N, Ulahannan SV, Colleoni M, Aftimos P, Donoghue MTA, Rosen E, Rudneva VA, Telli ML, Domchek SM, Galsky MD, Hoyle M, Chappey C, Stewart R, Blake-Haskins JA, Yap TA. Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial. JAMA Oncol. 2023 Jan 1;9(1):29-39. doi: 10.1001/jamaoncol.2022.5218. Erratum In: JAMA Oncol. 2023 Jul 1;9(7):1009.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03565991
• Other Study ID Numbers: B9991032; 2018-000345-39 ( EudraCT Number )
• First Submitted: May 25, 2018
• First Posted: June 21, 2018
• Results First Submitted: March 22, 2023
• Results First Posted: August 7, 2023
• Last Update Posted: September 25, 2023