Clinical Trial - NCT03330405

       

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

Active, not recruiting

Sponsor: Pfizer

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03330405

Protocol Info

Short Description:
Long Description: 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
MGH Status: Never Activated
Sponsor: Pfizer
Disease Program: Phase I

Next Steps


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Purpose

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 Title Intervention Phase
Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Pri Avelumab Phase 1b Talazoparib Phase 1b Avelumab Phase 2 Talazoparib Phase 2 Phase 2
Study Type Interventional
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

Primary Outcome Measures

Dose Limiting Toxicity (DLT) [Time Frame: Cycle 1 Days 1-28 (28 days from date of first dose of study treatment)] [Designated as safety issue: ]

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] [Designated as safety issue: ]


Secondary Outcome Measures

Serum concentrations of avelumab [Time Frame: Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1] [Designated as safety issue: ]

Anti drug antibody (ADA) levels of avelumab [Time Frame: Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1] [Designated as safety issue: ]

OR [Time Frame: From the start of treatment until disease progression/recurrence up to approximately 24 months] [Designated as safety issue: ]

PSA Tumor Marker [Time Frame: Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment ( up to approximately 24 months)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

Biomarker PD-L1 [Time Frame: Baseline] [Designated as safety issue: ]

Genomic [Time Frame: Baseline] [Designated as safety issue: ]

Serum concentrations of avelumab [Time Frame: Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1] [Designated as safety issue: ]

Plasma concentrations of talazoparib [Time Frame: Day 1 Cycles 1-4 and Day 15 Cycle 1] [Designated as safety issue: ]

Plasma concentration of talazoparib [Time Frame: Day 1 Cycles 1-4 and Day 15 Cycle 1] [Designated as safety issue: ]

Neutralizing antibodies (Nab) levels against avelumab. [Time Frame: Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1] [Designated as safety issue: ]

Time to Tumor Response (TTR) [Time Frame: Baseline up to approximately 24 months] [Designated as safety issue: ]

Duration of response (DR) [Time Frame: Baseline up to approximately 24 months] [Designated as safety issue: ]

Progression-Free Survival (PFS) [Time Frame: Baseline up to approximately 24 months] [Designated as safety issue: ]

Prostate-Specific Antigen (PSA) response [Time Frame: Baseline up to approximately 24 months] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: Baseline up to approximately 24 months] [Designated as safety issue: ]

Biomarker Tumor Mutational Burden [Time Frame: Baseline] [Designated as safety issue: ]

Estimated Enrollment: 216
Study Start Date: October 2017
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2021
Arms Assigned Interventions

Experimental:Dose Level 0 Phase 1b

Drug: Avelumab Drug: Talazoparib

Experimental:Dose Level -1 Phase 1b

Drug: Avelumab Drug: Talazoparib
Drug:Talazoparib Phase 1b
Talazoparib

Experimental:Dose Level -2 Phase 1b

Drug: Avelumab Drug: Talazoparib

Experimental:A1. NSCLC Phase 2

Drug: Avelumab Drug: Talazoparib
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.

Experimental:A2. NSCLC PD-L1 Resistant DDR+ Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:B1. TNBC Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:B2. HR+BC DDR Defect +Assay Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:C1. Ovarian CA Recurrent Plat-Sensitive Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:C2.Ovarian CA Recurrent Plat-Sensitive BRCA defect Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:D.Urothelial CA Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:E1. CRPC Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:E2. CRPC DDR Defect +Assay Phase 2

Drug: Avelumab Drug: Talazoparib

Experimental:F: Advanced Solid Tumors with BRCA or ATM defect Phase 2

Drug: Avelumab Drug: Talazoparib

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly 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-a, 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT03330405

Locations

  • United States, Arkansas
    • Highlands Oncology Group Fayetteville, Arkansas, United States, 72703
    • Highlands Oncology Group Rogers, Arkansas, United States, 72758
    • Highlands Oncology Group 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: 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 Laura and Isaac Perlmutter Cancer Center New York, New York, United States, 10016
    • 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 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
    • 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, Kaluga Region
    • 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
  • Russian Federation,
    • 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, Other
    • University College London Hospitals NHS Foundation Trust London, Other, United Kingdom, W1T 7HA
  • United Kingdom,
    • 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

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03330405
Other Study ID Numbers: 2017-001509-33
Study First Received:
Last Updated:
Health Authority:

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

Talazoparib

Antibodies, Monoclonal

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on January 20, 2021