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

A PHASE 1B/2 STUDY TO EVALUATE SAFETY AND ANTI TUMOR ACTIVITY OF AVELUMAB IN COMBINATION WITH THE POLY(ADENOSINE DIPHOSPHATE [ADP]-RIBOSE) POLYMERASE (PARP) INHIBITOR TALAZOPARIB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03330405

Enrollment

223

Registered

2017-11-06

Start date

2017-10-19

Completion date

2023-01-04

Last updated

2023-10-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Primary or Recurrent) or Metastatic Solid Tumors

Keywords

NSCLC, TNBC, hormone receptor positive (HR+) breast cancer, recurrent epithelial ovarian cancer, UC, and castration resistant prostate cancer (CRPC).

Brief summary

Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).

Detailed description

Avelumab is a human immunoglobulin (Ig)G1 monoclonal antibody (mAb) directed against programmed death ligand 1 (PD L1). Avelumab selectively binds to PD L1 and competitively blocks its interaction with programmed death receptor 1 (PD 1), thereby interfering with this key immune checkpoint inhibition pathway. Avelumab is currently being investigated as single agent and in combination with other anti cancer therapies in patients with locally advanced or metastatic solid tumors and various hematological malignancies. Talazoparib is a potent, orally bioavailable poly (adenosine diphosphate \[ADP\] ribose) polymerase (PARP) inhibitor, which is cytotoxic to human cancer cell lines harboring gene mutations that compromise deoxyribonucleic acid (DNA) repair, an effect referred to as synthetic lethality, and by trapping PARP protein on DNA thereby preventing DNA repair, replication, and transcription. Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).

Interventions

DRUGAvelumab Phase 1b

Avelumab

DRUGTalazoparib Phase 1b

Talazoparib

DRUGAvelumab Phase 2

The dose will be determined after the overall available data (including safety and preliminary anti tumor activity) emerging from the Phase 1b portion of the study have been evaluated.

DRUGTalazoparib Phase 2

The dose will be determined after the overall available data (including safety and preliminary anti tumor activity) emerging from the Phase 1b portion of the study have been evaluated.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent in adult patients with: NSCLC, TNBC, HR+ breast cancer, recurrent platinum sensitive ovarian cancer, UC, CRPC, and other advanced solid tumors with a BRCA or ATM gene defect * Mandatory primary or metastatic tumor biopsy. If archival tumor tissue is available from a biopsy/surgery the tumor tissue may be submitted without repeating a tumor biopsy during the screening period. * Minimum age in Japan is 20 years. * ECOG performance status 0 or 1. * Resolved acute effects of prior therapy * Adequate bone marrow, renal, and liver function. * Negative serum pregnancy test at screening. * Pregnant, breastfeeding females or female patients able to have children must agree to use highly effective method of contraception throughout the study and for at least 30 days after the last dose of avelumab and for at least 7 months after the last dose of talazoparib; fertile male patients must use a condom during treatment and for at least 4 months after the last dose of talazoparib. * Signed and dated informed consent.

Exclusion criteria

* Prior treatment with a PARP inhibitor. * Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, OX 40, GITR, LAG 3, IDO, TDO,TIM 3, CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. Prior treatment with Sipuleucel-T for patients with mCRPC is allowed. For cohort A2 NSCLC patients prior treatment with anti-PD-1/L1 is allowed * Prior anti-cancer therapy within 2 weeks prior to study enrollment. Prior radiation therapy within 2 weeks prior to enrollment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 2 days prior to study enrollment and no clinically significant toxicities are expected (eg, mucositis, esophagitis). * Major surgery within 4 weeks prior to study enrollment. * Current use of immunosuppressive medication at the time of study enrollment. * Known prior or suspected hypersensitivity to investigational products. * Known history of immune mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis. * Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. * Prior organ transplantation including allogenic stem-cell transplantation. * Vaccination within 4 weeks of study enrollment and while on trial is prohibited except for administration of inactivated vaccines. * Diagnosis of Myelodysplastic Syndrome. * Patients with known brain metastases requiring steroids. * Participation in other studies involving investigational drug(s) within 4 weeks prior to study participation and/or during study participation. * Persisting toxicity related to prior therapy \>Grade 1 * Known HIV or AIDs-related illness. * Positive HBV or HCV test indicating acute or chronic infection. * Active infection requiring systemic therapy. * Clinically significant cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study entry; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication. * Current or anticipated use within 7 days prior to first dose of study drug, or anticipated use during the study of a strong P-gp inhibitor. * Other acute or chronic medical or psychiatric conditions.

Design outcomes

Primary

Measure	Time frame	Description
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)	Cycle 1; 28 days	DLTs=occurrence of any of the following AEs attributable to any study treatment in Cycle 1:Hematologic: grade(G)4 neutropenia lasting \>5 days (absolute neutrophil count \[ANC\]\< 0.5\10\^9/L); febrile neutropenia; neutropenic infection (ANC\<1.0\10\^9/L, and G\>3 infection); G\>=3 thrombocytopenia (platelet count \[PC\] \<50.0\10\^9/L) with bleeding; G4 thrombocytopenia (PC\<25.0\10\^9/L); G4 anemia (life-threatening; urgent intervention indicated). Non-hematologic: G\>=3 toxicities unless predefined in the protocol; potential Hy's law cases. Non-adherence to treatment schedule: failure to deliver at least 75% of the planned doses of talazoparib during the first cycle of treatment due to treatment-related toxicities; G3 non-hematologic toxicity that delayed administration of either study drug for more than 2 weeks. Dose reductions: any adverse event (AE) that resulted in a dose reduction of talazoparib.
Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)	This outcome measure (OM) is reported for participants with solid tumors except mCRPC; for those participants, OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version(v) 1.1 by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-progressive disease (PD), where PD is unequivocal progression of pre-existing lesions.
Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment	From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)	This OM is reported for participants with mCRPC; for those participants, OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per PCWG3 criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.

Secondary

Measure	Time frame	Description
Number of Participants With TEAEs Leading to Discontinuation of Either Study Drug	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	Either study drug = avelumab only or talazoparib only. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Number of Participants With TEAEs Leading to Discontinuation of All Study Drugs	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	All study drugs = all study drugs in the combination. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Number of Participants With TEAEs Leading to Death	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first.
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. NCI-CTCAE criteria version 4.03 is used. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Trough Concentrations (Ctrough)/Predose and Maximum Concentrations (Cmax) of Serum Avelumab Concentrations (μg/mL) by Visit (Excluding Site 1055)	Predose/0 Hour (H) and 1 H on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4, and additionally on Day 1 of Cycles 6, 9, 12, 18, and 24.	Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle.
Predose and Postdose Plasma Talazoparib Concentrations (pg/mL) by Visit (Excluding Site 1055)	Pre-dose and post-dose (at the end of the avelumab infusion) on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4.	Pharmacokinetics (PK) data analyses included descriptive summary statistics of the pre-dose/Ctrough concentrations for both investigational products and post-dose (for talazoparib) or Cmax concentrations (for avelumab) for each cycle. Cmax=maximum concentration. Ctrough=trough concentration. Participants with moderate renal impairment were started at a lower, 0.75 mg QD, dose to compensate for decreased talazoparib clearance.
Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycle 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)	Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively.
Number of Participants by ADA Categories	Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycles 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)	Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA Result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively. n=number of participants in each category.
Phase 1b: Percentage of Participants With Confirmed OR as Per RECIST v1.1 and PCWG3 by Investigator Assessment	From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)	This OM is reported for participants in Phase 1b; OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.
Phase 1b: Time to Response (TTR) in Participants With Confirmed CR or PR	From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<=5.2 years approximately)	For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	Adverse event (AE) was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).
Phase 2: Duration of Response (DR) in Participants With Confirmed CR or PR	From the first objective tumor response/soft tissue response to the first objective tumor progression/subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first (<=5.2 years approximately)	For participants with solid tumors except mCRPC, DR was defined for participants with confirmed OR (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.
Phase 1b: Progression-Free Survival (PFS) in Participants With Confirmed CR or PR	From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)	For participants with solid tumors except mCRPC, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first
Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1)	From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)	This OM is reported for participants with solid tumors except mCRPC; for those participants, PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first.
Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1 and PCWG3)	From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)	This OM was reported for participants with mCRPC; for these participants, PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using RECIST v1.1, in bone as assessed by Investigator using PCWG3, or death, whichever occurred first.
Phase 2: Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC	From the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented (maximum up to 5.2 years approximately)	Time to PSA progression for participants with mCRPC was defined as the time from the first dose to the date that a \>=25% increase in PSA with an absolute increase of \>=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained \>=3 weeks (21 days) later.
Phase 1b: Overall Survival	From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)	Overall survival (OS) was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
Phase 2: Overall Survival	From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)	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.
Phase 2: Percentage of Participants With PSA Response	From baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50% (maximum up to 5.2 years approximately)	PSA response was defined as the proportion of participants with confirmed PSA decline \>=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must be confirmed by a second consecutive value at least 3 weeks later.
Phase 1b: Percentage of Participants With CA-125 Response	From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)	Cancer Antigen 125 (CA-125) response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
Phase 2: Percentage of Participants With CA-125 Response	From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)	CA-125 response is defined as at least a 50% reduction in CA-125 levels from baseline. The response must be confirmed and maintained for at least 28 days.
Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)	PD-L1 expression on tumor and infiltrating immune cells were measured by immunohistochemistry (IHC). PD-L1 expression level corresponds to the percentage of positive cells. The PD-L1 Positive category does not apply to cohorts A1 and A2. The PD-L1 High/Low categories only apply to cohorts A1 and A2. Participants were considered positive if their baseline tumor tissue sample demonstrated cell surface PD-L1 expression: 1) for Cohorts E1, E2, and F: \>=1% tumor cells (TC) or \>= 5% immune cells (IC); 2) for Cohort D: TC/IC\>=25%; 3) for Cohorts B1, B2, C1, C2: IC\>=5%; otherwise were considered negative. Categories based on PD-L1 expression level ≥50% and \<50% were defined as High and Low, respectively.
Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)	TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. High: TMB score \>=20 muts/mb (number of mutations per megabase of DNA); Medium: TMB score \>=10 muts/mb and \<20 muts/mb; Low: TMB score \<10 muts/mb.
Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)	DDR defect positive was determined by presence of one or more pathogenic or likely pathogenic mutations in tissue, DNA and/or blood samples.
Phase 2: TTR in Participants With Confirmed CR or PR	From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<= 5.2 years approximately)	For participants with solid tumors except mCRPC, TTR was defined for participants with confirmed OR (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC, TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a best overall response (BOR) of CR or PR as assessed by Investigator using RECIST v1.1.
Number of Participants With Grade >=3 TEAEs	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with Grade 3 or higher TEAEs were reported.
Number of Participants With Serious TEAEs	From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)	TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs). A serious TEAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/considered to be an important medical event: death; life-threatening experience (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect.

Countries

Australia, Belgium, Canada, Denmark, Hungary, Russia, South Korea, United Kingdom, United States

Participant flow

Recruitment details

The study was conducted in 2 phases: Phase 1b (talazoparib dose level cohorts) and Phase 2 (expansion phase). The Phase 1b study design started at the highest dose of talazoparib (1 mg QD), to be de-escalated to 0.75 and 0.5 mg QD. With DLT rate \<33% among 12 DLT-evaluable patients treated at 1 mg, Phase 2 started. The 2 cohorts at lower dose did not enroll any participants and are not displayed in the results. Only the Phase 1b cohort Avelumab 800 mg Q2W + Talazoparib 1 mg QD is displayed.

Pre-assignment details

Phase 1b: 12 participants were enrolled and assigned to study treatment. Phase 2: 211 participants were enrolled and assigned to study treatment.

Participants by arm

Arm	Count
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD Participants with locally advanced or metastatic solid tumors were treated with talazoparib 1.0 mg orally once daily (QD) in combination with avelumab 800 mg intravenously (IV) every 2 weeks (Q2W) for a maximum of 246.3 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	12
Phase 2: Cohort A1 (NSCLC) Participants with locally advanced (primary or recurrent) or metastatic non-small cell lung cancer (NSCLC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 183.6 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	42
Phase 2: Cohort A2 (NSCLC DDR+) Participants with locally advanced (primary or recurrent) or metastatic NSCLC with DNA damage repair positive (DDR+) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 173.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	5
Phase 2: Cohort B1 (TNBC) Participants with locally advanced (primary or recurrent) or triple-negative breast cancer (TNBC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 93.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	22
Phase 2: Cohort B2 (BC HR+ HER2- DDR+) Participants with locally advanced (primary or recurrent) or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 180.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	23
Phase 2: Cohort C1 (OVC) Participants with locally advanced (primary or recurrent) or metastatic ovarian cancer (OVC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 161.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	20
Phase 2: Cohort C2 (OVC BRCA-mutated) Participants with locally advanced (primary or recurrent) or metastatic OVC with germline or somatic BRCA1 or BRCA2 gene defect were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 144.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	11
Phase 2: Cohort D (UC) Participants with locally advanced (primary or recurrent) or metastatic urothelial cancer (UC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 164.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	40
Phase 2: Cohort E1 (mCRPC) Participants with metastatic castration-resistant prostate cancer (mCRPC) were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 54.1 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	21
Phase 2: Cohort E2 (mCRPC DDR+) Participants with mCRPC with DDR+ were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 74.0 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	18
Phase 2: Cohort F (BRCA/ATM-mutated) Participants with locally advanced (primary or recurrent) or metastatic solid tumors, independent of tissue of origin, with previously identified pathogenic, or likely pathogenic, germline or somatic defects in BRCA1, BRCA2, or ATM genes were treated with talazoparib 1 mg QD orally in combination with avelumab 800 mg IV Q2W for a maximum of 49.9 weeks. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	9
Total	223

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010
Overall Study	Adverse Event	0	1	0	1	1	1	3	4	2	2	2
Overall Study	Death	0	4	0	0	0	1	0	2	0	0	0
Overall Study	Global deterioration of health status	2	3	0	2	3	3	0	2	8	4	1
Overall Study	Other	1	3	1	0	2	0	1	0	0	0	0
Overall Study	Physician Decision	0	0	0	0	0	0	0	1	0	0	0
Overall Study	Progressive disease	8	27	4	18	16	14	7	29	9	11	5
Overall Study	Withdrawal by Subject	1	4	0	1	1	1	0	2	2	1	1

Baseline characteristics

Characteristic	Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Phase 2: Cohort A1 (NSCLC)	Phase 2: Cohort A2 (NSCLC DDR+)	Phase 2: Cohort B1 (TNBC)	Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Phase 2: Cohort C1 (OVC)	Phase 2: Cohort C2 (OVC BRCA-mutated)	Phase 2: Cohort D (UC)	Phase 2: Cohort E1 (mCRPC)	Phase 2: Cohort E2 (mCRPC DDR+)	Phase 2: Cohort F (BRCA/ATM-mutated)	Total
Age, Continuous Mean	62.67 Years STANDARD_DEVIATION 9.49	67.00 Years STANDARD_DEVIATION 9.37	59.60 Years STANDARD_DEVIATION 7.4	56.18 Years STANDARD_DEVIATION 12.49	53.83 Years STANDARD_DEVIATION 14.08	62.65 Years STANDARD_DEVIATION 10.66	61.36 Years STANDARD_DEVIATION 9.24	65.73 Years STANDARD_DEVIATION 9.19	63.71 Years STANDARD_DEVIATION 7.4	71.56 Years STANDARD_DEVIATION 7.37	63.00 Years STANDARD_DEVIATION 10.91	63.17 Years STANDARD_DEVIATION 11.04
Age, Customized 65 - <75 years	5 Participants	19 Participants	1 Participants	6 Participants	3 Participants	5 Participants	3 Participants	16 Participants	12 Participants	8 Participants	2 Participants	80 Participants
Age, Customized <65 years	6 Participants	15 Participants	4 Participants	15 Participants	17 Participants	12 Participants	7 Participants	16 Participants	8 Participants	3 Participants	5 Participants	108 Participants
Age, Customized 75 - <85 years	1 Participants	7 Participants	0 Participants	1 Participants	3 Participants	3 Participants	1 Participants	7 Participants	1 Participants	6 Participants	2 Participants	32 Participants
Age, Customized >= 85 years	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	3 Participants
ECOG Performance Status 0	4 Participants	5 Participants	1 Participants	12 Participants	12 Participants	9 Participants	8 Participants	16 Participants	4 Participants	6 Participants	1 Participants	78 Participants
ECOG Performance Status 1	8 Participants	37 Participants	4 Participants	10 Participants	11 Participants	11 Participants	3 Participants	24 Participants	17 Participants	12 Participants	8 Participants	145 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	3 Participants	1 Participants	0 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants	39 Participants	5 Participants	19 Participants	21 Participants	18 Participants	11 Participants	38 Participants	11 Participants	16 Participants	8 Participants	198 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	3 Participants	0 Participants	3 Participants	1 Participants	2 Participants	0 Participants	0 Participants	7 Participants	1 Participants	1 Participants	18 Participants
Geographic Region Asia	0 Participants	4 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	2 Participants	0 Participants	1 Participants	0 Participants	10 Participants
Geographic Region Australasia	0 Participants	0 Participants	0 Participants	2 Participants	2 Participants	3 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	10 Participants
Geographic Region Eastern Europe	0 Participants	19 Participants	0 Participants	6 Participants	4 Participants	5 Participants	1 Participants	16 Participants	0 Participants	1 Participants	0 Participants	52 Participants
Geographic Region North America	12 Participants	9 Participants	3 Participants	14 Participants	15 Participants	10 Participants	7 Participants	15 Participants	20 Participants	11 Participants	8 Participants	124 Participants
Geographic Region Western Europe	0 Participants	10 Participants	2 Participants	0 Participants	1 Participants	2 Participants	1 Participants	5 Participants	1 Participants	4 Participants	1 Participants	27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Asian	0 Participants	5 Participants	0 Participants	1 Participants	1 Participants	0 Participants	3 Participants	2 Participants	1 Participants	2 Participants	0 Participants	15 Participants
Race/Ethnicity, Customized Black or African American	3 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	5 Participants	2 Participants	0 Participants	14 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Not reported	0 Participants	2 Participants	0 Participants	1 Participants	4 Participants	2 Participants	0 Participants	1 Participants	3 Participants	0 Participants	0 Participants	13 Participants
Race/Ethnicity, Customized White	9 Participants	34 Participants	4 Participants	20 Participants	17 Participants	18 Participants	6 Participants	36 Participants	12 Participants	14 Participants	9 Participants	179 Participants
Sex: Female, Male Female	3 Participants	9 Participants	2 Participants	22 Participants	22 Participants	20 Participants	11 Participants	14 Participants	0 Participants	0 Participants	3 Participants	106 Participants
Sex: Female, Male Male	9 Participants	33 Participants	3 Participants	0 Participants	1 Participants	0 Participants	0 Participants	26 Participants	21 Participants	18 Participants	6 Participants	117 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk
deaths Total, all-cause mortality	6 / 12	33 / 42	3 / 5	16 / 22	16 / 23	11 / 20	6 / 11	26 / 40	16 / 21	14 / 18	7 / 9
other Total, other adverse events	12 / 12	41 / 42	5 / 5	21 / 22	22 / 23	20 / 20	10 / 11	38 / 40	21 / 21	16 / 18	9 / 9
serious Total, serious adverse events	1 / 12	16 / 42	2 / 5	7 / 22	5 / 23	9 / 20	2 / 11	16 / 40	5 / 21	9 / 18	4 / 9

Outcome results

Primary

Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)

DLTs=occurrence of any of the following AEs attributable to any study treatment in Cycle 1:Hematologic: grade(G)4 neutropenia lasting \>5 days (absolute neutrophil count \[ANC\]\< 0.5\*10\^9/L); febrile neutropenia; neutropenic infection (ANC\<1.0\*10\^9/L, and G\>3 infection); G\>=3 thrombocytopenia (platelet count \[PC\] \<50.0\*10\^9/L) with bleeding; G4 thrombocytopenia (PC\<25.0\*10\^9/L); G4 anemia (life-threatening; urgent intervention indicated). Non-hematologic: G\>=3 toxicities unless predefined in the protocol; potential Hy's law cases. Non-adherence to treatment schedule: failure to deliver at least 75% of the planned doses of talazoparib during the first cycle of treatment due to treatment-related toxicities; G3 non-hematologic toxicity that delayed administration of either study drug for more than 2 weeks. Dose reductions: any adverse event (AE) that resulted in a dose reduction of talazoparib.

Time frame: Cycle 1; 28 days

Population: The DLT analysis set was a subset of the safety analysis set and included all enrolled participants in the Phase 1b portion who were eligible for the study, received at least 1 dose of the combination treatment, and either experienced DLT during the first cycle (28 days) of treatment, or completed the DLT observation period for the first cycle of treatment.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)	3 Participants

Primary

Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment

This OM is reported for participants with mCRPC; for those participants, OR was defined as the proportion of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 and with no evidence of confirmed bone disease progression per PCWG3 criteria by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-PD.

Time frame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)

Population: The FAS included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was not planned to be collected and analyzed for Phase 1b arm. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm	Measure	Value (NUMBER)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment	0 Percentage of Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment	11.1 Percentage of Participants
Phase 2: Cohort B1 (TNBC)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment	50.0 Percentage of Participants

Primary

Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment

This outcome measure (OM) is reported for participants with solid tumors except mCRPC; for those participants, OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version(v) 1.1 by investigator. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis \<10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-progressive disease (PD), where PD is unequivocal progression of pre-existing lesions.

Time frame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)

Population: The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this OM was not planned to be collected and analyzed for Phase 1b arm. Here 'number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm	Measure	Value (NUMBER)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	16.7 Percentage of Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	20.0 Percentage of Participants
Phase 2: Cohort B1 (TNBC)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	18.2 Percentage of Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	34.8 Percentage of Participants
Phase 2: Cohort C1 (OVC)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	20.0 Percentage of Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	63.6 Percentage of Participants
Phase 2: Cohort D (UC)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	15.0 Percentage of Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	0 Percentage of Participants

Secondary

Number of Participants by ADA Categories

Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA Result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively. n=number of participants in each category.

Time frame: Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycles 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)

Population: The immunogenicity analysis set was a subset of the safety analysis set and included participants who had at least 1 ADA/Nab sample collected for avelumab. Cohorts in Phase 2 were combined as pre-specified in reporting and analysis plan.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants by ADA Categories	ADA ever-positive: Baseline ADA positive (n/N1) (No treatment-boosted ADA [n/N2])	0 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants by ADA Categories	ADA ever-positive (n/N0)	0 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants by ADA Categories	ADA ever-positive: Treatment-induced ADA positive (n/N3)	0 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants by ADA Categories	ADA never-positive (n/N0)	12 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants by ADA Categories	ADA ever-positive: Treatment-induced ADA positive (n/N3)	2 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants by ADA Categories	ADA ever-positive (n/N0)	6 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants by ADA Categories	ADA ever-positive: Baseline ADA positive (n/N1) (No treatment-boosted ADA [n/N2])	4 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants by ADA Categories	ADA never-positive (n/N0)	205 Participants

Secondary

Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)

Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline was defined as the last assessment prior to the date/time of the first dose of avelumab. N0, N1, N2, and N3=Number of participants with at least 1 valid ADA result at any time point, baseline (pre-dose on Day 1), baseline and post-baseline, and post-baseline, respectively.

Time frame: Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycle 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N0	12 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N1	12 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N2	11 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N3	11 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N3	200 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N0	211 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N2	202 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)	N1	209 Participants

Secondary

Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline

DDR defect positive was determined by presence of one or more pathogenic or likely pathogenic mutations in tissue, DNA and/or blood samples.

Time frame: At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)

Population: The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study treatment. Data for this outcome measure was presented for Phase 2 only as pre-specified in reporting and analysis plan.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	12 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	30 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	2 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	3 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	10 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	12 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	19 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	4 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	5 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	15 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	1 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	10 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	18 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	22 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	13 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	7 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	1 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	2 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	16 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Positive	8 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Unknown	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline	Negative	1 Participants

Secondary

Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline

PD-L1 expression on tumor and infiltrating immune cells were measured by immunohistochemistry (IHC). PD-L1 expression level corresponds to the percentage of positive cells. The PD-L1 Positive category does not apply to cohorts A1 and A2. The PD-L1 High/Low categories only apply to cohorts A1 and A2. Participants were considered positive if their baseline tumor tissue sample demonstrated cell surface PD-L1 expression: 1) for Cohorts E1, E2, and F: \>=1% tumor cells (TC) or \>= 5% immune cells (IC); 2) for Cohort D: TC/IC\>=25%; 3) for Cohorts B1, B2, C1, C2: IC\>=5%; otherwise were considered negative. Categories based on PD-L1 expression level ≥50% and \<50% were defined as High and Low, respectively.

Time frame: At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	22 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	9 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	3 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	0 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	8 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	1 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	1 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	0 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	1 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	2 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	8 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	6 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	8 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	16 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	4 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	3 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	2 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	13 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	5 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	5 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	4 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	2 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	19 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	8 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	13 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	1 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	13 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	7 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	2 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	12 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	4 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Negative	3 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	High	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Unknown	6 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Low	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline	Positive (Not applicable for Cohorts A1 and A2)	0 Participants

Secondary

Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline

TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. High: TMB score \>=20 muts/mb (number of mutations per megabase of DNA); Medium: TMB score \>=10 muts/mb and \<20 muts/mb; Low: TMB score \<10 muts/mb.

Time frame: At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	4 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	9 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	13 Participants
Phase 1b: Avelumab 800 mg Q2W + Talazoparib 1 mg QD	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	16 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	1 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	1 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	0 Participants
Phase 2: Cohort A2 (NSCLC DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	3 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	3 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	0 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	12 Participants
Phase 2: Cohort B1 (TNBC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	7 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	0 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	2 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	20 Participants
Phase 2: Cohort B2 (BC HR+ HER2- DDR+)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	1 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	12 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	1 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	7 Participants
Phase 2: Cohort C1 (OVC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	0 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	6 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	2 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	0 Participants
Phase 2: Cohort C2 (OVC BRCA-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	3 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	4 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	22 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	9 Participants
Phase 2: Cohort D (UC)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	5 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	10 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	11 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	3 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	2 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	13 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Low	8 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	High	0 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Unknown	1 Participants
Phase 2: Cohort F (BRCA/ATM-mutated)	Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline	Medium	0 Participants

Secondary

Number of Participants With Grade >=3 TEAEs

AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with Grade 3 or higher TEAEs were reported.