Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSISSYNOPSIS
Study Title: A Phase 2 Study to Evaluate Safety and Anti-tumor Activity of Avelumab in
Combination With Talazoparib in Patients With BRCA or ATM Mutant Tumors
Study Number: B9991032
Regulatory Agency or Public Disclosure Identifier Number:
US IND: 133,902, EudraCT: 2018-000345-39, NCT03565991
Study Phase: 2
Name of Study Intervention: Avelumab
Trade Name: BAVENCIO®
Name of Sponsor/Company: Pfizer Inc.
CSR Version and Report Date:
Document Version
Final CSR (LPLV Date) Version
1.0

Report Date
21 June 2023

Number of Study Center(s) and Investigator(s):A total of 202 participants were enrolled at 42 centers in 9 countries.
A list of study centers and investigators involved in this study is provided inAppendix 16.1.4.1.
Publications:Hyman David Michael, Zelnak Amelia B., Bauer Todd Michael, et al. JAVELIN
BRCA/ATM: A phase 2 trial of avelumab (anti–PD-L1) plus talazoparib (PARP inhibitor) inpatients with advanced solid tumors with a BRCA1/2 or ATM defect Journal of ClinicalOncology 2019;37 15_ Suppl:TPS2660.
Schram AM, Colombo N, Arrowsmith E, et al. 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 Oncology
2023;9(1):29-39.

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Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSIS
Study Period:First Participant First Visit (FPFV): 18 June 2018
Last Participant Last Visit (LPLV): 03 February 2023
This study was terminated.
Rationale:
This was a Phase 2 study to assess the safety and efficacy of the avelumab plus talazoparibcombination in up to approximately 200 patients with locally advanced (primary or recurrent)or metastatic solid tumors with a pathogenic or likely pathogenic germline or somatic breast
cancer susceptibility gene (BRCA)1, BRCA2, or ataxia telangiectasia mutated (ATM) genedefect, as determined by local assessment and classification. Patients with these gene defects
have limited therapeutic options after their disease has progressed on standard of care (SOC)
chemotherapy.
Avelumab is a human immunoglobulin (IgG)1 monoclonal antibody (mAb) directed against
programmed death ligand 1 (PD-L1). Avelumab selectively binds to PD-L1 andcompetitively blocks its interaction with programmed death receptor 1 (PD-1), thereby
interfering with this key immune checkpoint pathway.
Talazoparib is a potent, orally bioavailable poly (adenosine diphosphate-ribose) polymerase(PARP) inhibitor, which is cytotoxic to human cancer cell lines harboring gene mutations
that compromise DNA repair, an effect referred to as synthetic lethality, by inhibiting PARP
catalytic activity and trapping PARP protein on DNA, thereby preventing DNA repair,
replication, and transcription.
It was anticipated that patients with tumors harboring defects in the BRCA1, BRCA2, orATM gene would likely benefit from treatment with the combination of avelumab plus
talazoparib, independent of their tumor type, and that the combination might produce
additive or synergistic anti-tumor activity relative to each drug used as a single agent.
Objectives and Endpoints:
Type
Primary

Objective

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Endpoints

Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSIS
Type
Efficacy

Secondary
SafetyObjective
To evaluate objective response
rate (ORR) of avelumab in
combination with talazoparib, inparticipants with locally advanced
or metastatic solid tumors
harboring BRCA1, BRCA2 or
ATM defect.

Endpoints
Confirmed objective response(OR) in participants with locallyadvanced or metastatic solid
tumors with BRCA 1/2 or ATM
defect, as assessed by blinded
independent central review(BICR), using Response
Evaluation Criteria in Solid
Tumors, version 1.1 (RECISTv1.1) and, in participants withmetastatic castration resistant
prostate cancer (mCRPC),
RECIST v1.1 and Prostate Cancer
Working Group 3 (PCWG3)(bone).

To assess the overall safety andtolerability of avelumab in
combination with talazoparib.

Adverse events (AEs) as
characterized by type,severity (as graded by
National Cancer Institute[NCI] Common Terminology
Criteria for Adverse Events[CTCAE] v.4.03), timing,
seriousness, and relationshipto study therapy.



Laboratory abnormalities ascharacterized by type,severity (as graded by NCI
CTCAE v.4.03) and timing.

Pharmacokinetics (PK)To characterize the PK ofavelumab and talazoparib when
given in combination.

Immunogenicity

To evaluate the immunogenicity
of avelumab when given in
combination with talazoparib.

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PK parameters including:
pre-dose/trough concentrations(Ctrough) for avelumab andtalazoparib, post-doseconcentrations for talazoparib, andmaximum concentration (Cmax) for
avelumab.
Avelumab anti-drug antibody(ADA) levels and neutralizing
antibody (NAb) against avelumab.

Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSIS
Type
Efficacy

Objective
To assess other measures of theanti-tumor activity of avelumab in
combination with talazoparib.

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Endpoints
 Confirmed OR as assessed by
the investigator, using
RECIST v1.1 and, inparticipants with mCRPC,RECIST v1.1 and PCWG3.
Time to event endpoints:
Endpoints as assessed by
BICR and as assessed by theinvestigator, using RECIST
v1.1 and in participants with
mCRPC, RECIST v1.1 andPCWG3, including time toresponse (TTR), duration of
response (DoR), andprogression free survival(PFS). Additional
time-to-event endpoints
include overall survival (OS)for all participants and time toprostate specific antigen(PSA) progression(25% increase) for mCRPC
participants.



PSA response 50% decrease
and circulating tumor cell(CTC) count conversion forparticipants with mCRPC.



Cancer antigen 125 (CA-125)
response 50% decrease forparticipants with ovariancancer.

Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSISType
Biomarker

Objective To assess the correlation ofanti-tumor activity ofavelumab in combination
with talazoparib with PD-L1
expression in baseline tumor
tissue.

Endpoints
 PD-L1 expression level inbaseline tumor tissue.



To assess the correlation ofanti-tumor activity andemergence of resistance withdefects in a panel of key
oncogenes, including
BRCA1/2 and ATM, andtumor mutational burden(TMB) in circulating tumor
DNA (ctDNA) and tumor
tissue at baseline, during
treatment and at the end oftreatment.

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Page 5Presence of defects in a panelof key oncogenes, including
BRCA 1/2 and ATM, and
TMB in ctDNA and tumor
tissue at baseline, during
treatment, and at the end oftreatment.

Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSIS
Type

Objective

Endpoints
.

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Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSIS
Methodology:
This was a Phase 2, open-label, multi-center, non-randomized study of avelumab in
combination with talazoparib in adult participants with locally advanced or metastatic solid
tumors with a pathogenic or likely pathogenic germline or loss-of-function somatic BRCA1
or BRCA2, or ATM gene defect, as determined by local assessment and classification, whohave received at least 1 line of SOC treatment for locally advanced or metastatic disease
unless prior treatment requirements are otherwise specified. Two cohorts were enrolled inparallel:

Cohort 1 was to enroll up to approximately 150 participants with locally advanced ormetastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes;

Cohort 2 was to enroll up to approximately 50 participants with locally advanced ormetastatic solid tumors with one or more defects in the ATM gene.
Note: in the event that a participant had concomitant defects in more than 1 of thethree genes (BRCA1 or BRCA2 or ATM), they were to be enrolled in Cohort 1.

Number of Participants (planned and analyzed):
Planned: Up to approximately 150 participants were to be enrolled in Cohort 1 and 50
participants in Cohort 2. Thus, a total of approximately 200 participants were to be enrolled.
Analyzed: A total of 200 out of 202 enrolled participants received at least 1 dose of study
drug; 159 in Cohort 1 and 41 in Cohort 2.
Diagnosis and Main Criteria for Inclusion and Exclusion:
Enrolled in this study were participants with tumors harboring defects in the BRCA1,
BRCA2, or ATM gene. Participants had to have measurable disease by RECIST v1.1
(non-measurable disease was only allowed in participants with mCRPC).
Study Interventions, Dose, Mode of Administration, and Batch Number(s):All participants were assigned to receive a fixed dose of avelumab 800 mg every 2 weeks(Q2W) intravenously and oral talazoparib at 1 mg once daily (QD) or 0.75 mg QD forparticipants with moderate renal impairment at baseline.

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Final Abbreviated Clinical Study Report
Protocol B9991032

CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Intervention(s) Administered
Investigational Product Description
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
MSB0010718C Solution for Infusion,
20 mg/mL (10 mL/vial)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
MSB0010718C Solution for Infusion,
20 mg/mL (10 mL/vial)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
MSB0010718C Solution for Infusion,
20 mg/mL (10 mL/vial)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
MSB0010718C Solution for Infusion, 20
mg/mL (10 mL/vial)
MSB0010718C Solution for Infusion, 20
mg/mL (10 mL/vial)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)
Talazoparib 1 mg Bottle 30 ct.
(MDV3800 Capsules)

Vendor Lot
No.

Pfizer Lot
No.

Strength/Potency

DosageForm

170851917-003337

1 mg

Capsules

PD1G003

16-003176

200 mgSolution

1707899

17-003251

1 mg

CapsulesPD1H001/2

18-000308

200 mgSolution

181011918-002600

1 mg

Capsules1800870

18-000623

1 mg

Capsules

PD1J004

18-003041

200 mgSolution

1807947

18-001962

1 mg

Capsules1813425

18-004049

1 mg

Capsules1912494

19-003198

1 mg

Capsules

PD1J008

19-000790

200 mgSolution

PD1J005

19-000003

200 mgSolution

181343118-004057

1 mg

Capsules1905903

19-002206

1 mg

Capsules

1708520

17-003337

1 mg

Capsules1800874

18-000627

1 mg

Capsules

1807950

18-001965

1 mg

CapsulesDuration of Study Intervention:
Treatment with avelumab and talazoparib would continue until disease progression was
confirmed by the investigator (except where treatment was allowed beyond progression),
participant refusal, unacceptable toxicity, or until the study was terminated by the sponsor,
whichever occurred first.

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Protocol B9991032

CLINICAL STUDY REPORT SYNOPSIS
Summary of Results:
Demographic and Other Baseline Characteristics:
There were 108 (67.9%) females and 51 (32.1%) males in Cohort 1. The median (range) age
was 57 years (26, 84). One hundred and ten (69.2%) participants were under 65 years. The
majority of participants (117 [73.6%]) were White.
There were 24 (58.5%) females and 17 (41.5%) males in Cohort 2. The median (range) age
was 61 years (32, 89). Twenty-five (61.0%) participants were under 65 years and 2 (4.9%)
participants were over 85 years. The majority of participants (37 [90.2%]) were White.
Various solid tumors were enrolled in this study. In Cohort 1, the most common (≥5% ofparticipants) enrolled tumor types were HR+ HER2- BC (16.4%), CRPC (16.4%), ovariancancer (germ cell tumors excluded) (16.4%), TNBC (15.7%), pancreatic cancer (islet cell andcarcinoid tumors excluded) (10.1%), colorectal cancer (5.0%) and cholangiocarcinoma(5.0%). In Cohort 2, the most common (≥5% of participants) enrolled tumor types werecolorectal cancer (22.0%), HR+ HER2- BC (14.6%), CRPC (12.2%), pancreatic cancer (islet
cell and carcinoid tumors excluded) (12.2%), ovarian cancer (7.3%), and endometrial cancer(7.3%).
Exposure:
In Cohort 1, the median duration of treatment with avelumab was 22.9 weeks with a medianof 10 infusions. The median duration of treatment with talazoparib was 23.1 weeks.
In Cohort 2, the median duration of treatment with avelumab was 16 weeks with a median of
8 infusions. The median duration of treatment with talazoparib was 16.4 weeks.
Efficacy Results:
The confirmed ORR based on BICR assessment was:

27.7% (95% confidence interval [CI]: 20.9%, 35.3%) in Cohort 1, with 11
participants achieving complete response (CR) and 33 participants achieving partial
response (PR).



7.3% (95% CI: 1.5%, 19.9%) in Cohort 2, with 3 participants achieving PR.

The confirmed ORR based on investigator assessment was:

34.6% (95% CI: 27.2%, 42.5%) in Cohort 1, with 8 participants achieving CR and47 participants achieving PR.



14.6% (95% CI: 5.6%, 29.2%) in Cohort 2, with 6 participants achieving PR.

The agreement rate between BICR and investigator assessments of objective response was
88.1% and 87.8% in Cohorts 1 and 2, respectively.
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CLINICAL STUDY REPORT SYNOPSIS
Based on BICR assessment, the posterior probabilities of ORR ≥40% (prespecified target)
were 0.059 and <0.001 for Cohorts 1 and 2, respectively.
In Cohort 1, for the 127 participants with measurable disease at baseline, the ORR based on
BICR assessment was 33.1% (95% CI: 25.0%, 42.0%). One hundred and twenty-two
participants had BRCA-dependent tumor types (defined as breast, ovarian, prostate, andpancreatic cancers, and uterine leiomyosarcoma) and 37 participants had
non-BRCA-dependent cancer types. Responses were more frequent in participants with
BRCA-dependent tumor types (ORR: 33.6% [95% CI: 25.3%, 42.7%]) compared with
non-BRCA-dependent tumor types (ORR: 8.1% [95% CI: 1.7%, 21.9%]). For the 51
participants with BC, the ORR was 51.0% (95% CI: 36.6%, 65.2%).
In Cohort 1, the ORR was numerically higher for participants with germline vs somatic
tumor BRCA1/2 alterations: 31.0% (18 participants, 95% CI: 19.5%, 44.5%) vs 10.0% (1participant, 95% CI: 0.3%, 44.5%), respectively.
Based on BICR assessment,

In Cohort 1, the median DoR was 12.5 months (95% CI: 7.5, NE).

In Cohort 2, the DoR was 6.7 months for the only responder with subsequent
progression.

For participants who had an OR as assessed by BICR, the median TTR was 1.8 months(range: 1.5, 12.1) for Cohort 1. In Cohort 2, the median TTR for the 3 responders was 5.5
months (range: 1.6, 16.8).
Based on investigator assessment,

In Cohort 1, the median DoR was 8.8 months (95% CI: 7.5, 10.7).



In Cohort 2, the median DoR was 7.1 months (95% CI: 5.5, 9.7).

For participants who had an OR as assessed by investigator, the median TTR was 1.8 months(range: 1.5, 18.4) for Cohort 1. In Cohort 2, median TTR was 4.0 months (range: 1.9, 14.0).
Median PFS based on BICR assessment was 3.7 months (95% CI: 3.1, 5.4) in Cohort 1 and3.5 months (95% CI: 1.8, 5.5) in Cohort 2.
Median PFS based on investigator assessment was 5.3 months (95% CI: 3.7, 5.6) in Cohort 1
and 3.7 months (95% CI: 2.1, 7.4) in Cohort 2.
Median OS was 11.9 months (95% CI: 10.1, 13.7) in Cohort 1 and 16.4 months (95% CI:
12.8, 21.9) in Cohort 2.

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Safety Results:
Overall, 136 (68.0%) participants experienced Grade ≥3 all-causality treatment-emergent
adverse events (TEAEs) and 102 (51.0%) participants experienced Grade ≥3treatment-related TEAEs. Serious TEAEs were reported in 57 (28.5%) participants and weretreatment-related in 16 (8.0%) participants. The overall rate of all-causality andtreatment-related TEAEs leading to discontinuations of either avelumab or talazoparib waslow (<5%). Immune-related adverse events (irAEs) were reported in 27 (13.5%) participants
and infusion-related reactions (IRRs) were reported in 42 (21.0%) participants. There wereno treatment-related TEAEs leading to death.
Overall, the most frequently reported TEAEs (≥30% of participants) were anaemia (50.0%),
nausea (47.0%) and fatigue (34.5%). The most frequently reported Grade ≥3 TEAEs (≥5% ofparticipants) were anaemia (36.5%), platelet count decreased (8.0%), thrombocytopenia(8.0%), neutropenia (7.5%), fatigue (6.0%) and disease progression (5.0%).
Overall, the most frequently reported treatment-related TEAEs (≥20% of participants) were
anaemia (45.5%), nausea (32.5%), and fatigue (24.0%). The most frequently reported Grade≥3 treatment-related TEAEs (≥5% of participants) were anaemia (34.5%), thrombocytopenia(8.0%), platelet count decreased (7.5%), and neutropenia (7.0%).
A total of 152 (76.0%) participants died. The most frequently reported cause of death was
disease progression (121 participants [60.5%]). No deaths were attributed to study treatment
toxicity.
A total of 16 (8.0%) participants had TEAEs leading to death. The most frequently reported
TEAEs leading to death was disease progression (10 participants [5.0%]). All other TEAEs
leading to death were reported in single participant.
A total of 57 (28.5%) participants had serious adverse events (SAEs). The most frequently
reported SAEs (≥2% of participants) were disease progression (10 participants [5.0%]),anaemia (6 participants [3.0%]) and pneumonia (5 participants [2.5%]). A total of 16 (8.0%)
participants had treatment-related SAEs. The most frequently reported treatment-related SAE(≥2% of participants) was anaemia (6 participants [3.0%]).
A total of 8 (4.0%) participants had TEAEs leading to discontinuation of avelumab only,
including 7 (3.5%) with treatment-related events; 4 (2.0%) participants had TEAEs leading todiscontinuation of talazoparib only with all being treatment-related. The most frequent TEAE
leading to discontinuation of avelumab only was arthralgia in 2 participants (1.0%) and themost frequent TEAE leading to discontinuation of talazoparib only was anaemia in 2
participants (1.0%).
A total of 7 (3.5%) participants had TEAEs leading to permanent discontinuation of all study
drugs. The most frequently reported TEAE leading to permanent discontinuation of all study
drugs was intestinal obstruction (2 participants [1.0%]). No other TEAEs leading todiscontinuation was reported in more than 1 participant. One participant had a
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Final Abbreviated Clinical Study Report
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CLINICAL STUDY REPORT SYNOPSIS
treatment-related TEAE leading to discontinuation of all study drugs (drug-induced liver
injury).
A total of 27 (13.5%) participants had AEs classified as irAEs, including 6 (3.0%) with
Grade ≥3 irAEs. The most frequently reported irAE (≥ 5%) by Cluster was Immune-related
Thyroid disorders (15 participants [7.5%]). The most frequently reported Grade ≥3 irAE(≥2%) by Cluster was Immune-related Hepatitis (4 participants [2.0%]).
Serious irAEs were reported in 4 participants (2.0%). The serious irAEs included alanine
aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased,
immune-mediated hepatitis, drug-induced liver injury, hepatic enzyme increased andmyositis. None of the serious irAEs were reported in more than 2 participants.
A total of 42 (21.0%) participants had IRRs. One participant had Grade 3 IRR; no otherparticipants had Grade ≥3 IRRs. One participant in Cohort 1 had a serious IRR. There wereno Grade 5 IRRs.
Pharmacokinetic Results:
Avelumab:Mean and median avelumab Ctrough (0 H) and Cmax (1 H) concentrations were consistent withpreviously reported Ctrough and Cmax concentrations following avelumab 10 mg/kg Q2W
monotherapy. The avelumab exposure for 800 mg flat dose in this study was less variable
than the body weight-based dosing regimen of 10 mg/kg Q2W. Serum trough concentrationsof avelumab appeared to be at steady state at Cycle 3 and beyond.
Talazoparib:
The geometric mean of Ctrough at Cycle 3 Day 1 was 3.31 ng/mL with a 95% CI of (2.36,
4.65) ng/mL which is within the range of historical data for talazoparib Ctrough at steady statefor 1 mg QD dosing (3.53 ng/mL). The pre-dose and post-dose concentrations of talazoparibwere similar between the 1 mg (normal/mild renal impairment) and 0.75 mg (moderate renal
impairment) dose groups.
Immunogenicity Results:
Of the 199 participants with at least 1 valid ADA result at any time point, 192 (96.5%) were
ADA never-positive. Of the 7 (3.5%) ADA ever-positive participants, 6 were baseline ADA
positive, and only 1 participant had a treatment-induced transient ADA response. No
participant experienced a treatment-boosted ADA response. ADA never-positive rate was
96.2% and 97.5% for Cohort 1 (BRCA1/2 defect) and Cohort 2 (ATM defect), respectively.
Due to the low observed immunogenicity rate, NAb analysis was not conducted.

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CLINICAL STUDY REPORT SYNOPSIS

Conclusions:
Efficacy:Various solid tumors were enrolled in this study. In Cohort 1 (BRCA1/2 defect), themost common (≥5% of participants) enrolled tumor types were HR+ HER2- BC(16.4%), CRPC (16.4%), ovarian cancer (germ cell tumors excluded) (16.4%), TNBC
(15.7%), pancreatic cancer (islet cell and carcinoid tumors excluded) (10.1%),
colorectal cancer (5.0%) and cholangiocarcinoma (5.0%). In Cohort 2 (ATM defect),the most common (≥5% of participants) enrolled tumor types were colorectal cancer(22.0%), HR+ HER2- BC (14.6%), CRPC (12.2%), pancreatic cancer (islet cell andcarcinoid tumors excluded) (12.2%), ovarian cancer (7.3%), and endometrial cancer(7.3%).

In Cohort 1 (BRCA1/2 defect), the ORR was 27.7% (95% CI: 20.9%, 35.3%) basedon BICR assessment and 34.6% (95% CI: 27.2%, 42.5%) based on investigatorassessment. Antitumor activity for the combination therapy was mainly observed in
BRCA-dependent tumor types (ie, breast, ovarian, prostate, pancreatic cancers anduterine leiomyosarcoma) (ORR: 33.6% [95% CI: 25.3%, 42.7%] vs ORR in
non-BRCA-dependent tumor types: 8.1% [95% CI: 1.7%, 21.9%], which was
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comparable with that reported for PARP inhibitor monotherapy). The median DoR
was 12.5 months (95% CI: 7.5, NE) based on BICR assessment and 8.8 months (95%
CI: 7.5, 10.7) based on investigator assessment.


In Cohort 2 (ATM defect), the ORR was 7.3% (95% CI: 1.5%, 19.9%) based on
BICR assessment and 14.6% (95% CI: 5.6%, 29.2%) based on investigatorassessment. Overall, participants enrolled in the ATM cohort had limited clinicalbenefit from the treatment with the avelumab plus talazoparib combination. Becauseof the low clinical activity, enrollment of Cohort 2 was closed after 41 participants
were treated. The DoR was 6.7 months based on BICR assessment for the only
evaluable responder and the median DoR was 7.1 months (95% CI: 5.5, 9.7) based oninvestigator assessment.

Neither Cohort 1 nor Cohort 2 met the prespecified target ORR of 40%, indicatingthat a pan-cancer tumor-agnostic approach with this combination is not an optimal
clinical strategy.

Safety:The safety profile of avelumab at 800 mg Q2W in combination with talazoparib 1 mg
QD was consistent with the known safety profile of each drug with no new safety
signals observed for avelumab or talazoparib. The toxicities were generally
manageable with low rate (<5%) of any study drug discontinuation.



The incidence of Grade ≥3 irAEs and serious irAEs was generally low (3.0% and2.0%, respectively). There were no Grade 5 irAEs.

PK and Immunogenicity:

There was no evidence of any PK drug-drug interaction between talazoparib andavelumab, and avelumab treatment-emergent ADA incidence in presence oftalazoparib was low.

Biomarkers:
In Cohort 1, the ORR was numerically higher for participants with germline vssomatic tumor BRCA1/2 alterations.

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