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

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 JAVELIN BRCA/ATM

Avelumab in combination with talazoparib will be investigated in patients with locally advanced or metastatic solid tumors with a BRCA or ATM defect.

Study Overview

• Status: Terminated
• Conditions: Locally Advanced or Metastatic Solid Tumors; Genes, BRCA 1
• Intervention / Treatment: Drug: Avelumab; Drug: Talazoparib

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 with a BReast CAncer susceptibility gene (BRCA)1, or BRCA2, or ataxia telangiectasia mutated (ATM) gene defect.

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Odense C, Denmark, 5000
    • Odense University Hospital
• France
  • Clermont Ferrand, France, 63000
    • Centre Jean Perrin
  • La Rochelle, France, 17000
    • Groupe Hospitalier La Rochelle-Ré-Aunis
  • Montpellier Cedex 5, France, 34298
    • Institut Regional du Cancer de Montpellier - ICM Val d'Aurelle
• Italy
  • Napoli, Italy, 80131
    • Fondazione Pascale, IRCCS, Istituto Nazionale dei Tumori
  • Roma, Italy, 00161
    • Azienda Policlinico Umberto I, Universita La Sapienza, Oncologia B
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli Unità di Farmacologia Clinica
  • AN
    • Torette Di Ancona, AN, Italy, 60123
      • Presidio AO-U, Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi
  • FC
    • Meldola, FC, Italy, 47014
      • IRCCS-Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
  • MB
    • Monza, MB, Italy, 20900
      • Azienda Socio-Sanitaria Territoriale Monza, Ospedale San Gerardo
  • MI
    • Milano, MI, Italy, 20133
      • Fondazione IRCCS, Istituto Nazionale dei Tumori
    • Milano, MI, Italy, 20141
      • Istituto Europeo di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Osaka
    • Osaka-shi, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Netherlands
  • Noord Holland
    • Amsterdam, Noord Holland, Netherlands, 1081 HV
      • Amsterdam University Medical Centre, location VUmc
  • Zuid-holland
    • Rotterdam, Zuid-holland, Netherlands, 3015 GD
      • Erasmus Universitair Medisch Centrum
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28009
    • H.G.U. Gregorio Marañón
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28040
    • H.U. Fundación Jiménez Díaz
  • Sevilla, Spain, 41014
    • Hospital Universitario Virgen de Valme
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust, St Bartholomew's Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford Women's Cancer Center
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
    • Stanford, California, United States, 94305
      • Stanford Healthcare
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Atlanta Cancer Care -Alpharetta
    • Athens, Georgia, United States, 30606
      • Northside Hospital, Inc. - GCS/Athens
    • Atlanta, Georgia, United States, 30341
      • Northside Hospital, Inc. - GCS/Annex
    • Atlanta, Georgia, United States, 30342
      • Atlanta Cancer Care - Atlanta
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital, Inc. - Central Research Department
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital, Inc. - GCS/Northside
    • Canton, Georgia, United States, 30114
      • Northside Hospital, Inc. - GCS/Canton
    • Cumming, Georgia, United States, 30041
      • Atlanta Cancer Care - Cumming
    • Decatur, Georgia, United States, 30033
      • Atlanta Cancer Care - Decatur
    • Decatur, Georgia, United States, 30033
      • Northside Hospital, Inc.-GCS/Stemmer
    • Jonesboro, Georgia, United States, 30236
      • Atlanta Cancer Care - Stockbridge
    • Macon, Georgia, United States, 31217
      • Northside Hospital, Inc.-GCS/Macon
    • Marietta, Georgia, United States, 30060
      • Northside Hospital, Inc.-GCS/Kennestone
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center - West County
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center - South County
    • Saint Louis, Missouri, United States, 63110
      • Washington University Infusion Center Pharmacy
    • Saint Louis, Missouri, United States, 63136
      • Siteman Cancer Center - North County
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center - St.Peters
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Cancer Center- Monmouth
  • New York
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Cancer Center- Westchester
    • Long Island City, New York, United States, 11101
      • Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center
    • New York, New York, United States, 10016
      • NY Investigational Pharmacy
    • New York, New York, United States, 10022
      • Rockefeller Outpatient Center
    • New York, New York, United States, 10065
      • Memorial Hospital
    • New York, New York, United States, 10016
      • NYU Langone Radiology - 32nd Street
    • New York, New York, United States, 10017
      • NYU Langone Radiology Ambulatory Care Center East 41st Street
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).
    • New York, New York, United States, 10022
      • Rockefeller Outpatient Pavilion (53rd Street)
    • New York, New York, United States, 10065
      • Evelyn H. Lauder Breast and Imaging Center
    • White Plains, New York, United States, 10601
      • White Plains Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
    • Columbus, Ohio, United States, 43221
      • Martha Morehouse Medical Plaza
    • Columbus, Ohio, United States, 43212
      • Stephanie Spielman Comprehensive Breast Cancer
    • Hilliard, Ohio, United States, 43026
      • OSU Gynecologic Oncology at Mill Run
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania/Penn Investigational Drug Services
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn IDS Central
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Women's Hospital Women's Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center Investigational Drug Service
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology, PLLC
    • Chattanooga, Tennessee, United States, 37404
      • The Sarah Cannon Research Institute
    • Cleveland, Tennessee, United States, 37311
      • Tennessee Oncology, PLLC
    • Dickson, Tennessee, United States, 37055
      • Tennessee Oncology, PLLC
    • Franklin, Tennessee, United States, 37067
      • Tennessee Oncology, PLLC
    • Gallatin, Tennessee, United States, 37066
      • Tennessee Oncology, PLLC
    • Hermitage, Tennessee, United States, 37076
      • Tennessee Oncology, PLLC
    • Lebanon, Tennessee, United States, 37090
      • Tennessee Oncology, PLLC
    • Murfreesboro, Tennessee, United States, 37129
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37205
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37207
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37211
      • Tennessee Oncology, PLLC
    • Shelbyville, Tennessee, United States, 37160
      • Tennessee Oncology, PLLC
    • Smyrna, Tennessee, United States, 37167
      • Tennessee Oncology, PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BRCA1, BRCA2 and/or ATM gene defect.
• Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent
• Availability a tumor tissue sample from a diagnostic biopsy/surgery or a metastatic tumor biopsy.
• Progressive disease at study enrollment.
• Minimum age 18 years (in Japan, minimum age 20 years).
• ECOG performance status 0 or 1.
• Adequate bone marrow, renal and liver function.
• For childbearing female patients, negative serum or urine pregnancy test at screening
• Signed and dated informed consent document.

Exclusion Criteria:

• Prior anti-cancer therapy or radiation therapy within 2 weeks prior to enrolment. Palliative radiotherapy to metastatic lesion(s) permitted providing that it has been completed at least 2 days prior to enrolment and no significant toxicity are expected.
• Major surgery within 4 weeks prior to study enrollment.
• Current use of immunosuppressive medication at the time of study enrollment.
• Known prior severe hypersensitivity to investigational products or any component in their formulations
• 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.
• Administration of live attenuated vaccines within 4 weeks of study enrollment.
• Diagnosis of myelodysplastic syndrome.
• Known symptomatic brain metastases requiring steroids.
• Persisting toxicity related to prior therapy Grade >1.
• Known history of HIV or AIDS.
• Positive HBV or HCV test indicating acute or chronic infection.
• Active infection requiring systemic therapy.
• Clinically significant (active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study enrollment; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.
• Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast, bladder, or cervix, or low-grade prostate cancer or other early-stage low-risk cancers.
• Pregnant or breastfeeding female patients; female or male patients who are able to have children who are unable or unwilling to use contraception as outlined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination of avelumab and talazoparib; Single arm open label	Drug: Avelumab; IV treatment; Other Names: Bavencio; Drug: Talazoparib; Oral treatment; Other Names: MDV3800, BMN 673

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Confirmed Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)	For participants with solid tumors, except metastatic Castration Resistant Prostate Cancer (mCRPC), OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), both confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. For participants with mCRPC, OR was defined as the percentage of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria. Per RECIST v1.1, CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Non-target PR lesions must be non-Progressive Disease (PD), where PD was unequivocal progression of pre-existing lesions.	From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device. TEAEs were those events with onset dates occurring during the on-treatment period. A Serious Adverse Event (SAE) was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.	From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately
Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period	The laboratory results were graded according to the CTCAE v4.03 severity grade whenever applicable. Laboratory test abnormalities were summarized according to worst toxicity grade observed for each laboratory test. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day).	From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately
Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period	The laboratory results were graded according to the CTCAE v4.03 severity grade whenever applicable. Laboratory test abnormalities were summarized according to worst toxicity grade observed for each laboratory test. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day).	From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately
Serum Lowest (Trough) Concentration (Ctrough) of Avelumab	Ctrough was defined as predose concentration during multiple dosing. The determination method of Ctrough was observing directly from data. The lower limit of quantification (LLQ) was 0.2 mcg/mL. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented.	Predose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
Serum Maximum Concentration (Cmax) for Avelumab	Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.	One hour post-dose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
Plasma Ctrough for Talazoparib	Ctrough was defined as predose concentration during multiple dosing. The determination method of Ctrough was observing directly from data. The lower limit of quantification (LLQ) was 25 pg/mL. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented. Evaluable participants were participants with non-missing Ctrough concentrations at each specific time point and meeting 2 conditions: participants received 14 consecutive days of talazoparib dose without dosing interruption prior to sample collection (except on Cycle 1 Day 1) and sample collection within 24 hours ± 10% (2 hours and 24 minutes) after the previous day's dose and no more than 5 minutes (0.083 hours) after the administration of the dose on the day of PK sample collection. Predose PK samples on Cycle 1 Day 1 must have been collected prior to dose.	Predose on Cycle 1 Days 1, 15 and Cycle 3 Day 1
Plasma Post-dose Concentrations for Talazoparib	In this OM, the post-dose concentrations for talazoparib in plasma were reported.	Postdose (samples collected within 2 hours post dose plus/minus 12 minutes) on Days 1,15 of Cycle 1, and Day 1 of Cycle 3
Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories	Blood samples were assayed for ADA using a validated assay. ADA never-positive = no positive ADA results at any time point. ADA ever-positive =at least one positive ADA result at any time point. Baseline ADA positive =a positive ADA result at baseline. Treatment-boosted ADA =a positive ADA result at baseline and the titer >=8×baseline titer at least once after treatment with avelumab. Treatment-induced ADA = participant was ADA-negative at baseline and had at least one positive post-baseline ADA result; or the participant had at least one positive post-baseline ADA result if no baseline sample. Transient ADA response = participants with treatment-induced ADA had (a single positive ADA result or duration between first and last positive result <16 weeks) and ADA result at the last assessment was not positive. Persistent ADA response =participants with treatment-induced ADA had duration between first and last positive ADA result >=16 weeks or a positive ADA result at the last assessment.	Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
Number of Participants With Neutralizing Antibodies (Nab) Levels Against Avelumab Ever-Positive	Nab ever-positive was defined as at least one positive Nab result at any time point. Samples positive for ADA with persistent treatment-induced ADA response could be analyzed for Nab.	Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
Percentage of Participants With Confirmed OR as Assessed by The Investigator	For participants with solid tumors, except mCRPC, OR was defined as a CR or PR per RECIST v1.1, both confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. For participants with mCRPC, OR was defined as the percentage of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per PCWG3 criteria. Per RECIST v1.1, CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Non-target PR lesions must be non-PD, where PD was unequivocal progression of pre-existing lesions.	From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months
Time to Tumor Response (TTR) as Assessed by BICR	For participants with solid tumors, except mCRPC: TTR was defined for participants with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a Best Overall Response (BOR) of CR or PR per RECIST v1.1.	Baseline up to approximately 24 months
TTR as Assessed by Investigator	For participants with solid tumors, except mCRPC: TTR was defined for participants with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a BOR of CR or PR per RECIST v1.1.	Baseline up to approximately 24 months
Overall Survival (OS) for All Participants	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.	Baseline up to approximately 24 months
Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC	For participants with mCRPC, time to PSA progression was defined as the time from the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained >=3 weeks (21 days) later.	Baseline up to approximately 24 months
Number of Participants With Confirmed PSA Response	For participants with mCRPC, PSA response was defined as confirmed PSA decline >=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must have been confirmed by a second consecutive value at least 3 weeks later.	Baseline up to approximately 24 months
Number of Participants With Circulating Tumor Cell (CTC) Count Conversion	For participants with mCRPC, CTC count conversion was defined as a decrease in CTC count from >=5 CTC per 7.5 mL of blood at baseline to <5 CTC per 7.5 mL of blood anytime on study.	Day 1 of Cycle 1 to Cycle 4
Number of Participants With Cancer Antigen 125 (CA-125) Response	For participants with ovarian cancer, CA-125 response was defined as at least a 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.	Baseline, Day 1 of each treatment Cycle, maximum up to 4.3 years approximately
Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Expression in Baseline Tumor Tissue	PD-L1 expression on tumor and infiltrating immune cells was measured by immunohistochemistry (IHC). PD-L1 expression level was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. This OM reported the number of participants classified as positive according to scoring algorithms and cut-offs established from external sources.	Baseline
Number of Participants With Different Status for Defects in BRCA1, BRCA2 and ATM	Participants were enrolled in the two cohorts based on BRCA 1/2 and ATM defect status assessed by the local laboratory. The participant BRCA and ATM status was assessed retrospectively by central laboratory, that may differ from the status assessed by the local laboratory. The ATM participants with a negative ATM status per the central laboratory were reported to have a positive ATM status per the local laboratory. Therefore, participants with negative ATM status might have been included in the ATM defect cohort. For defects in BRCA1, BRCA2 and ATM by central laboratory analysis, participants were classified as positive, negative, not analyzable or missing. The number of participants in each category of BRCA 1 defect, BRCA 2 defect, BRCA 1 or BRCA 2 defect and ATM defect were presented.	Baseline
Number of Participants by Status of 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. TMB categories were defined as high, low for a number of mutations per megabase >=10 and <10, respectively. The TMB category 'Not analyzable' included participants with available samples but not evaluable. The TMB category 'Missing' included participants with no sample available. The number of participants in each category at only baseline were tabulated.	Baseline
Duration of Response (DoR) as Assessed by BICR	For participants with solid tumors, except mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occured first. For participants with mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occured first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3.	Baseline up to approximately 24 months
DoR as Assessed by Investigator	For participants with solid tumors, except mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. For participants with mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3.	Baseline up to approximately 24 months
Progression Free Survival (PFS) as Assessed by BICR	For participants with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first.	Baseline up to approximately 24 months
PFS as Assessed by Investigator	For participants with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first.	Baseline up to approximately 24 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

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

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2018
• Primary Completion (Actual): March 28, 2022
• Study Completion (Actual): February 3, 2023

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: BRCA, ATM
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Avelumab; Talazoparib
• Other Study ID Numbers: B9991032; 2018-000345-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No