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

Sponsor
Pfizer (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03330405
Collaborator
(none)
226
Enrollment
58
Locations
13
Arms
58.9
Anticipated Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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
  • 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
Actual Enrollment :
226 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 :
Oct 19, 2017
Actual Primary Completion Date :
Feb 22, 2022
Anticipated Study Completion Date :
Sep 16, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Level 0 Phase 1b

Drug: Avelumab Drug: Talazoparib

Drug: Avelumab Phase 1b
Avelumab
Other Names:
  • MSB0010718C

    • Drug: Talazoparib Phase 1b
    Talazoparib
    Other Names:
  • MDV3800, BMN 673

    		•
    Experimental: Dose Level -1 Phase 1b

    Drug: Avelumab Drug: Talazoparib

    Drug: Avelumab Phase 1b
    Avelumab
    Other Names:
  • MSB0010718C

    • Drug: Talazoparib Phase 1b
    Talazoparib
    Other Names:
  • MDV3800, BMN 673

    		•
    Experimental: Dose Level -2 Phase 1b

    Drug: Avelumab Drug: Talazoparib

    Drug: Avelumab Phase 1b
    Avelumab
    Other Names:
  • MSB0010718C

    • Drug: Talazoparib Phase 1b
    Talazoparib
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • MDV3800, BMN 673

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicity (DLT) [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)

    2. Overall Response (OR) [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

    Secondary Outcome Measures

    1. Serum concentrations of avelumab [Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1]

      Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)

    2. Anti drug antibody (ADA) levels of avelumab [Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1]

      Immunogenicity assessment of avelumab

    3. OR [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.

    4. PSA Tumor Marker [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.

    5. CA-125 Tumor Marker [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.

    6. Biomarker PD-L1 [Baseline]

      PD-L1 expression level in baseline tumor tissue.

    7. Genomic [Baseline]

      Genomic scarring and the presence of defects in select genes, considered critical to effective DDR, in baseline tumor tissue.

    8. Serum concentrations of avelumab [Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1]

      Pharmacokinetic parameters: maximum concentrations (Cmax)

    9. Plasma concentrations of talazoparib [Day 1 Cycles 1-4 and Day 15 Cycle 1]

      Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)

    10. Plasma concentration of talazoparib [Day 1 Cycles 1-4 and Day 15 Cycle 1]

      Pharmacokinetic parameters: post-dose concentrations

    11. Neutralizing antibodies (Nab) levels against avelumab. [Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1]

      Immunogenicity assessment of avelumab

    12. Time to Tumor Response (TTR) [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.

    13. Duration of response (DR) [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.

    14. Progression-Free Survival (PFS) [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.

    15. Prostate-Specific Antigen (PSA) response [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.

    16. Overall Survival (OS) [Baseline up to approximately 24 months]

      OS is defined as the time from the first dose of study treatment to the date of death.

    17. Biomarker Tumor Mutational Burden [Baseline]

      Tumor mutational burden in baseline tumor tissue

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Site City State Country Postal Code
    1 Highlands Oncology Group Fayetteville Arkansas United States 72703
    2 Highlands Oncology Group Rogers Arkansas United States 72758
    3 Highlands Oncology Group Springdale Arkansas United States 72762
    4 Tower Hematology Oncology Medical Group Beverly Hills California United States 90211
    5 Keck Hospital of USC Los Angeles California United States 90033
    6 LAC+USC Medical Center Los Angeles California United States 90033
    7 USC/Norris Comprehensive Cancer Center/Investigational Drug Services Los Angeles California United States 90033
    8 USC/Norris Comprehensive Cancer Center Los Angeles California United States 90033
    9 Cedars-Sinai Medical Center Los Angeles California United States 90048
    10 Hoag Memorial Hospital Presbyterian Newport Beach California United States 92663
    11 Freidenrich Center for Translational Research (CTRU) Palo Alto California United States 94304
    12 Stanford Cancer Institute Stanford California United States 94305
    13 Stanford Hospital and Clinics Stanford California United States 94305
    14 Stanford Women's Cancer Center Stanford California United States 94305
    15 Georgetown University Medical Center Washington District of Columbia United States 20007
    16 Massachusetts General Hospital (MGH) Boston Massachusetts United States 02114
    17 Massachusetts General Hospital Attn: Svetlana Rashkova Boston Massachusetts United States 02114
    18 Brigham & Women's Hospital Boston Massachusetts United States 02115
    19 Dana Farber Cancer Institute, Attn: Vasilika Koci, PharmD Boston Massachusetts United States 02215
    20 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    21 University Of Minesota Health: Clinics And Surgery Center Minneapolis Minnesota United States 55455
    22 University of Minesota Medical Center, Fairview IDS Pharmacy Minneapolis Minnesota United States 55455
    23 University of Minnesota Medical Center, Fairview Minneapolis Minnesota United States 55455
    24 Roswell Park Cancer Center Institute Buffalo New York United States 14263
    25 NYU Investigational Pharmacy New York New York United States 10016
    26 NYU Langone Medical Center New York New York United States 10016
    27 NYU Laura and Isaac Perlmutter Cancer Center New York New York United States 10016
    28 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    29 Mount Sinai Hospital- Pharmacy department New York New York United States 10029
    30 Cleveland Clinic Taussig Cancer Center Investigational Pharmacy Cleveland Ohio United States 44106
    31 Cleveland Clinic Cleveland Ohio United States 44195
    32 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    33 Macquarie University North Ryde New South Wales Australia 2109
    34 Northern Cancer Institute St. Leonards New South Wales Australia 2065
    35 Mater Misericordiae Ltd Brisbane Queensland Australia 4101
    36 Fiona Stanley Hospital Murdoch Western Australia Australia 6150
    37 Institut Jules Bordet Brussels Belgium 1000
    38 Cliniques Universitaires Saint-Luc Bruxelles Belgium 1200
    39 Grand Hôpital de Charleroi - Site Notre-Dame Charleroi Belgium 6000
    40 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    41 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    42 Phase 1 Unit, Department of Oncology, Section 5073. Copenhagen Denmark 2100
    43 The Experimental Cancer Therapy Unit Herlev Denmark 2730
    44 Orszagos Onkologiai Intezet Budapest Hungary H-1122
    45 CRU Hungary Kft. Miskolc Hungary 3529
    46 Pecsi Tudomanyegyetem Pecs Hungary H-7624
    47 Gachon University Gil Medical Center Incheon Korea, Republic of 21565
    48 Seoul National University Hospital Seoul Korea, Republic of 03080
    49 Asan Medical Center Seoul Korea, Republic of 05505
    50 Medical Radiological Research Center n.a. A.F. Tsyba - Obninsk Kaluga Region Russian Federation 249036
    51 Medical Radiological Research Center n.a. A.F. Tsyba Obninsk Kaluga Region Russian Federation 249036
    52 GBUZ Chelyabinsk Russian Federation 454087
    53 FSBI "National Medical Research Centre of Oncology n.a. Moscow Russian Federation 115478
    54 Budget Healthcare Institution of Omsk Region "Clinical Oncology Dispensary" Omsk Russian Federation 644013
    55 State budgetary institution of healthcare of Yaroslavl region "Clinical oncology hospital" Yaroslavl Russian Federation 150054
    56 University College London Hospitals NHS Foundation Trust London Other United Kingdom W1T 7HA
    57 University Hospitals of Leicester NHS Trust Leicester United Kingdom LE1 5WW
    58 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)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT03330405
    Other Study ID Numbers:
    • B9991025
    • 2017-001509-33
    • JAVELIN PARP MEDLEY
    First Posted:
    Nov 6, 2017
    Last Update Posted:
    May 31, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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

    Study Results

    No Results Posted as of May 31, 2022