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

• ClinicalTrials.gov Identifier: NCT03330405
• Recruitment Status: Terminated
• First Posted: November 6, 2017
• Results First Posted: June 12, 2023
• Last Update Posted: October 13, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Primary or Recurrent) or Metastatic Solid Tumors	Drug: Avelumab Phase 1b; Drug: Talazoparib Phase 1b; Drug: Avelumab Phase 2; Drug: Talazoparib Phase 2	Phase 1; Phase 2

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 223 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 19, 2017
• Actual Primary Completion Date: February 22, 2022
• Actual Study Completion Date: January 4, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Level 0 Phase 1b; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab Phase 1b; Avelumab; Other Name: MSB0010718C; Drug: Talazoparib Phase 1b; Talazoparib; Other Name: MDV3800, BMN 673
Experimental: Dose Level -1 Phase 1b; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab Phase 1b; Avelumab; Other Name: MSB0010718C; Drug: Talazoparib Phase 1b; Talazoparib; Other Name: MDV3800, BMN 673
Experimental: Dose Level -2 Phase 1b; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab Phase 1b; Avelumab; Other Name: MSB0010718C; Drug: Talazoparib Phase 1b; Talazoparib; Other Name: MDV3800, BMN 673
Experimental: A1. NSCLC Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: A2. NSCLC PD-L1 Resistant DDR+ Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: B1. TNBC Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: B2. HR+BC DDR Defect +Assay Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: C1. Ovarian CA Recurrent Plat-Sensitive Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: C2.Ovarian CA Recurrent Plat-Sensitive BRCA defect Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: D.Urothelial CA Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: E1. CRPC Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: E2. CRPC DDR Defect +Assay Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673
Experimental: F: Advanced Solid Tumors with BRCA or ATM defect Phase 2; Drug: Avelumab Drug: Talazoparib	Drug: Avelumab 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.; Other Name: MSB0010718C; Drug: Talazoparib 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.; Other Name: MDV3800, BMN 673

Outcome Measures

Primary Outcome Measures :

1. Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: 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.
2. 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 [ 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) ]
   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.
3. 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 [ 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) ]
   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 Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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).
2. Number of Participants With Grade >=3 TEAEs [ Time Frame: 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.
3. Number of Participants With Serious TEAEs [ Time Frame: 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.
4. Number of Participants With TEAEs Leading to Discontinuation of Either Study Drug [ Time Frame: 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).
5. Number of Participants With TEAEs Leading to Discontinuation of All Study Drugs [ Time Frame: 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).
6. Number of Participants With TEAEs Leading to Death [ Time Frame: 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.
7. Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period [ Time Frame: 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.
8. Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period [ Time Frame: 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.
9. Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period [ Time Frame: 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.
10. Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period [ Time Frame: 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.
11. Trough Concentrations (Ctrough)/Predose and Maximum Concentrations (Cmax) of Serum Avelumab Concentrations (μg/mL) by Visit (Excluding Site 1055) [ Time Frame: 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.
12. Predose and Postdose Plasma Talazoparib Concentrations (pg/mL) by Visit (Excluding Site 1055) [ Time Frame: 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.
13. 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) [ 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) ]
    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.
14. Number of Participants by ADA Categories [ 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) ]
    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.
15. Phase 1b: Percentage of Participants With Confirmed OR as Per RECIST v1.1 and PCWG3 by Investigator Assessment [ Time Frame: 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.
16. Phase 1b: Time to Response (TTR) in Participants With Confirmed CR or PR [ Time Frame: 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.
17. Phase 2: TTR in Participants With Confirmed CR or PR [ Time Frame: 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.
18. Phase 2: Duration of Response (DR) in Participants With Confirmed CR or PR [ Time Frame: 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.
19. Phase 1b: Progression-Free Survival (PFS) in Participants With Confirmed CR or PR [ Time Frame: 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
20. Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1) [ Time Frame: 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.
21. Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1 and PCWG3) [ Time Frame: 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.
22. Phase 2: Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC [ Time Frame: 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.
23. Phase 1b: Overall Survival [ Time Frame: 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.
24. Phase 2: Overall Survival [ Time Frame: 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.
25. Phase 2: Percentage of Participants With PSA Response [ Time Frame: 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.
26. Phase 1b: Percentage of Participants With CA-125 Response [ Time Frame: 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.
27. Phase 2: Percentage of Participants With CA-125 Response [ Time Frame: 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.
28. Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline [ Time Frame: 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.
29. Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline [ Time Frame: 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.
30. Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arkansas

Highlands Oncology Group

Fayetteville, Arkansas, United States, 72703

Highlands Oncology

Fayetteville, Arkansas, United States, 72703

Highlands Oncology Group

Rogers, Arkansas, United States, 72758

Highlands Oncology

Rogers, Arkansas, United States, 72758

Highlands Oncology Group

Springdale, Arkansas, United States, 72762

Highlands Oncology

Springdale, Arkansas, United States, 72762

United States, California

Tower Hematology Oncology Medical Group

Beverly Hills, California, United States, 90211

Keck Hospital of USC

Los Angeles, California, United States, 90033

LAC+USC Medical Center

Los Angeles, California, United States, 90033

USC/Norris Comprehensive Cancer Center/Investigational Drug Services

Los Angeles, California, United States, 90033

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

Freidenrich Center for Translational Research (CTRU)

Palo Alto, California, United States, 94304

Stanford Cancer Institute

Stanford, California, United States, 94305

Stanford Hospital and Clinics

Stanford, California, United States, 94305

Stanford Women's Cancer Center

Stanford, California, United States, 94305

United States, District of Columbia

Georgetown University Medical Center

Washington, District of Columbia, United States, 20007

United States, Massachusetts

Massachusetts General Hospital (MGH)

Boston, Massachusetts, United States, 02114

Massachusetts General Hospital Attn: Lalit Joshi

Boston, Massachusetts, United States, 02114

Massachusetts General Hospital Attn: Svetlana Rashkova

Boston, Massachusetts, United States, 02114

Brigham & Women's Hospital

Boston, Massachusetts, United States, 02115

Dana Farber Cancer Institute, Attn: Vasilika Koci, PharmD

Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Minnesota

University Of Minesota Health: Clinics And Surgery Center

Minneapolis, Minnesota, United States, 55455

University of Minesota Medical Center, Fairview IDS Pharmacy

Minneapolis, Minnesota, United States, 55455

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States, 55455

United States, New York

Roswell Park Cancer Center Institute

Buffalo, New York, United States, 14263

NYU Investigational Pharmacy

New York, New York, United States, 10016

NYU Langone Medical Center

New York, New York, United States, 10016

NYU Langone Radiology

New York, New York, United States, 10016

NYU Laura and Isaac Perlmutter Cancer Center

New York, New York, United States, 10016

NYU Langone Radiology - Ambulatory Care Center

New York, New York, United States, 10017

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Mount Sinai Hospital- Pharmacy department

New York, New York, United States, 10029

United States, Ohio

Cleveland Clinic Taussig Cancer Center Investigational Pharmacy

Cleveland, Ohio, United States, 44106

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Australia, New South Wales

Macquarie University

North Ryde, New South Wales, Australia, 2109

Northern Cancer Institute

St. Leonards, New South Wales, Australia, 2065

Northern Cancer Institute

Sydney, New South Wales, Australia, 2065

Australia, Queensland

Mater Misericordiae Ltd

Brisbane, Queensland, Australia, 4101

Australia, Western Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia, 6150

Belgium

Institut Jules Bordet

Brussels, Belgium, 1000

Cliniques Universitaires Saint-Luc

Bruxelles, Belgium, 1200

Grand Hôpital de Charleroi - Site Notre-Dame

Charleroi, Belgium, 6000

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Denmark

Phase 1 Unit, Department of Oncology, Section 5073.

Copenhagen, Denmark, 2100

Herlev og Gentofte Hospital

Herlev, Denmark, 2730

The Experimental Cancer Therapy Unit

Herlev, Denmark, 2730

Hungary

Orszagos Onkologiai Intezet

Budapest, Hungary, H-1122

CRU Hungary Kft.

Miskolc, Hungary, 3529

Pecsi Tudomanyegyetem

Pecs, Hungary, H-7624

Korea, Republic of

Gachon University Gil Medical Center

Incheon, Korea, Republic of, 21565

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Asan Medical Center

Seoul, Korea, Republic of, 05505

Russian Federation

Medical Radiological Research Center n.a. A.F. Tsyba -

Obninsk, Kaluga Region, Russian Federation, 249036

Medical Radiological Research Center n.a. A.F. Tsyba

Obninsk, Kaluga Region, Russian Federation, 249036

GBUZ

Chelyabinsk, Russian Federation, 454087

FSBI "National Medical Research Centre of Oncology n.a.

Moscow, Russian Federation, 115478

Budget Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"

Omsk, Russian Federation, 644013

State budgetary institution of healthcare of Yaroslavl region "Clinical oncology hospital"

Yaroslavl, Russian Federation, 150054

United Kingdom

University College London Hospitals NHS Foundation Trust

London, Other, United Kingdom, W1T 7HA

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom, LE1 5WW

Freeman Hospital, The Sir Bobby Robson Cancer Trials

Newcastle Upon Tyne, United Kingdom, NE7 7DN

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] November 20, 2018

Statistical Analysis Plan  [PDF] December 16, 2021

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yap TA, Bardia A, Dvorkin M, Galsky MD, Beck JT, Wise DR, Karyakin O, Rubovszky G, Kislov N, Rohrberg K, Joy AA, Telli ML, Schram AM, Conte U, Chappey C, Stewart R, Stypinski D, Michelon E, Cesari R, Konstantinopoulos PA. Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors: The JAVELIN PARP Medley Nonrandomized Controlled Trial. JAMA Oncol. 2023 Jan 1;9(1):40-50. doi: 10.1001/jamaoncol.2022.5228.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03330405
• Other Study ID Numbers: B9991025; 2017-001509-33 ( EudraCT Number ); JAVELIN PARP MEDLEY ( Other Identifier: Alias Study Number )
• First Posted: November 6, 2017
• Results First Posted: June 12, 2023
• Last Update Posted: October 13, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

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

Additional relevant MeSH terms:

Neoplasms; Avelumab; Talazoparib; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action