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

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ClinicalTrials.gov Identifier: NCT03330405
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 16, 2017
First Posted Date  ICMJE November 6, 2017
Last Update Posted Date May 1, 2019
Actual Study Start Date  ICMJE October 19, 2017
Estimated Primary Completion Date March 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2017)
  • Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 Days 1-28 (28 days from date of first dose of study treatment) ]
    Phase 1b: DLT during the DLT evaluation period (Cycle 1)
  • Overall Response (OR) [ Time Frame: From date of 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 ]
    Phase 2: Confirmed OR, as assessed by the Investigator using RECIST v1.1 in patients with locally advanced or metastatic solid tumors and RECIST v1.1 and PCWG3 in patients with metastatic CRPC
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03330405 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
  • Serum concentrations of avelumab [ Time Frame: Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
  • Anti drug antibody (ADA) levels of avelumab [ Time Frame: Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1 ]
    Immunogenicity assessment of avelumab
  • OR [ Time Frame: From the start of treatment until disease progression/recurrence up to approximately 24 months ]
    Phase 1b: Confirmed OR, as assessed by the Investigator using RECIST v1.1 in patients with locally advanced or metastatic solid tumors and RECIST v1.1 and PCWG3 in patients with metastatic CRPC.
  • PSA Tumor Marker [ Time Frame: Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment ( up to approximately 24 months) ]
    PSA response greater than or equal to 50% for patients with metastatic CRPC.
  • CA-125 Tumor Marker [ Time Frame: Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment (up to approximately 24 months) ]
    CA-125 response for patients with ovarian cancer.
  • Biomarker PD-L1 [ Time Frame: Baseline ]
    PD-L1 expression level in baseline tumor tissue.
  • Genomic [ Time Frame: Baseline ]
    Genomic scarring and the presence of defects in select genes, considered critical to effective DDR, in baseline tumor tissue.
  • Serum concentrations of avelumab [ Time Frame: Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: maximum concentrations (Cmax)
  • Plasma concentrations of talazoparib [ Time Frame: Day 1 Cycles 1-4 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
  • Plasma concentration of talazoparib [ Time Frame: Day 1 Cycles 1-4 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: post-dose concentrations
  • Neutralizing antibodies (Nab) levels against avelumab. [ Time Frame: Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1 ]
    Immunogenicity assessment of avelumab
  • Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 24 months ]
    Time to Tumor Response (TTR) is defined for patients 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.
  • Duration of response (DR) [ Time Frame: Baseline up to approximately 24 months ]
    Duration of Response (DR) is defined for patients with confirmed objective response (complete response [CR] or partial response [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 occurs first.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to approximately 24 months ]
    Progression Free Survival (PFS) is 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 occurs first.
  • Prostate-Specific Antigen (PSA) response [ Time Frame: Baseline up to approximately 24 months ]
    PSA response is defined as the proportion of patients with confirmed PSA decline greater than or equal to 50% compared to baseline.
  • Overall Survival (OS) [ Time Frame: Baseline up to approximately 24 months ]
    OS is defined as the time from the first dose of study treatment to the date of death.
  • Biomarker Tumor Mutational Burden [ Time Frame: Baseline ]
    Tumor mutational burden in baseline tumor tissue
Original Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2017)
  • Serum concentrations of avelumab [ Time Frame: Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
  • Anti drug antibody (ADA) levels of avelumab [ Time Frame: Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1 ]
    Immunogenicity assessment of avelumab
  • OR [ Time Frame: From the start of treatment until disease progression/recurrence up to approximately 24 months ]
    Phase 1b: Confirmed OR, as assessed by the Investigator using RECIST v1.1 in patients with locally advanced or metastatic solid tumors and RECIST v1.1 and PCWG3 in patients with metastatic CRPC.
  • PSA Tumor Marker [ Time Frame: Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment ( up to approximately 24 months) ]
    PSA response greater than or equal to 50% for patients with metastatic CRPC.
  • CA-125 Tumor Marker [ Time Frame: Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment (up to approximately 24 months) ]
    CA-125 response for patients with ovarian cancer.
  • Biomarker PD-L1 [ Time Frame: Baseline ]
    PD-L1 expression level in baseline tumor tissue.
  • Genomic [ Time Frame: Baseline ]
    Genomic scarring and the presence of defects in select genes, considered critical to effective DDR, in baseline tumor tissue.
  • Serum concentrations of avelumab [ Time Frame: Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: maximum concentrations (Cmax)
  • Plasma concentrations of talazoparib [ Time Frame: Day 1 Cycles 1-4 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
  • Plasma concentration of talazoparib [ Time Frame: Day 1 Cycles 1-4 and Day 15 Cycle 1 ]
    Pharmacokinetic parameters: post-dose concentrations
  • Neutralizing antibodies (Nab) levels against avelumab. [ Time Frame: Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1 ]
    Immunogenicity assessment of avelumab
  • Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 24 months ]
    Time to Tumor Response (TTR) is defined for patients 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.
  • Duration of response (DR) [ Time Frame: Baseline up to approximately 24 months ]
    Duration of Response (DR) is defined for patients with confirmed objective response (complete response [CR] or partial response [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 occurs first.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to approximately 24 months ]
    Progression Free Survival (PFS) is 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 occurs first.
  • Prostate-Specific Antigen (PSA) response [ Time Frame: Baseline up to approximately 24 months ]
    PSA response is defined as the proportion of patients with confirmed PSA decline greater than or equal to 50% compared to baseline.
  • Overall Survival (OS) [ Time Frame: Baseline up to approximately 24 months ]
    OS is defined as the time from the first dose of study treatment to the date of death.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors
Official Title  ICMJE 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
Brief Summary Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).
Detailed Description

Avelumab is a human immunoglobulin (Ig)G1 monoclonal antibody (mAb) directed against programmed death ligand 1 (PD L1). Avelumab selectively binds to PD L1 and competitively blocks its interaction with programmed death receptor 1 (PD 1), thereby interfering with this key immune checkpoint inhibition pathway. Avelumab is currently being investigated as single agent and in combination with other anti cancer therapies in patients with locally advanced or metastatic solid tumors and various hematological malignancies.

Talazoparib is a potent, orally bioavailable poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor, which is cytotoxic to human cancer cell lines harboring gene mutations that compromise deoxyribonucleic acid (DNA) repair, an effect referred to as synthetic lethality, and by trapping PARP protein on DNA thereby preventing DNA repair, replication, and transcription.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Primary or Recurrent) or Metastatic Solid Tumors
Intervention  ICMJE
  • Drug: Avelumab Phase 1b
    Avelumab
    Other Name: MSB0010718C
  • Drug: Talazoparib Phase 1b
    Talazoparib
    Other Name: MDV3800, BMN 673
  • 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
Study Arms  ICMJE
  • Experimental: Dose Level 0 Phase 1b

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 1b
    • Drug: Talazoparib Phase 1b
  • Experimental: Dose Level -1 Phase 1b

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 1b
    • Drug: Talazoparib Phase 1b
  • Experimental: Dose Level -2 Phase 1b

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 1b
    • Drug: Talazoparib Phase 1b
  • Experimental: A1. NSCLC Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: A2. NSCLC PD-L1 Resistant DDR+ Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: B1. TNBC Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: B2. HR+BC DDR Defect +Assay Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: C1. Ovarian CA Recurrent Plat-Sensitive Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: C2.Ovarian CA Recurrent Plat-Sensitive BRCA defect Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: D.Urothelial CA Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: E1. CRPC Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: E2. CRPC DDR Defect +Assay Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
  • Experimental: F: Advanced Solid Tumors with BRCA or ATM defect Phase 2

    Drug: Avelumab

    Drug: Talazoparib

    Interventions:
    • Drug: Avelumab Phase 2
    • Drug: Talazoparib Phase 2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 21, 2018)
242
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2017)
296
Estimated Study Completion Date  ICMJE March 28, 2020
Estimated Primary Completion Date March 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Denmark,   Hungary,   Korea, Republic of,   Russian Federation,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03330405
Other Study ID Numbers  ICMJE B9991025
2017-001509-33 ( EudraCT Number )
JAVELIN PARP MEDLEY ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP