Talazoparib and Avelumab in Participants With Metastatic Renal Cell Carcinoma

Completed · Phase 2

Conditions studied: Metastatic Renal Cell Carcinoma, Fumarate Hydratase Deficient Renal Cell Carcinoma, Succinate Dehydrogenase Deficient Renal Cell Carcinoma

In brief

The purpose of this study is to see whether the combination of avelumab and talazoparib can be an effective treatment for metastatic renal cell carcinoma.

Key facts

Study ID: NCT04068831
Run by: Memorial Sloan Kettering Cancer Center
People needed: 18
Starts: 2019-08-22
Expected to finish: 2023-12-06
Last updated by the study team: 2024-12-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Biopsy proven, histological confirmed renal cell carcinoma (RCC) or renal medullary carcinoma (RMC).. Patients with surgery and biopsy at outside institutions will be eligible for this protocol once archival material is reviewed and the above diagnosis confirmed by genitourinary pathology review at Memorial Sloan Kettering Cancer Center (MSKCC).
Cohort 1: (Closed to Accrual)
Presence of VHLalteration by next-generation sequencing (NGS) with a stateapproved assay
Patients must have radiographic evidence of disease progression after treatment with at least one prior PD-1 or PD-L1 agent, and one prior VEGF inhibitor
Maximum 3 prior lines of therapy
Cohort 2:
For FH/SDH patients FH- or SDH- expression-loss by immunohistochemistry (IHC) or alteration (somatic or germline) in FH or SDH per NGS with a state-approved assay
For Renal Medullary Carcinoma (RMC) patients: histologic confirmation of RMC (no IHC/NGS criteria required)
At least one prior line of therapy:
For FH/SDH patients Patients must have radiographic evidence of disease progression after treatment with at least one prior line of therapy (one prior PD-1/PD-L1 and/or VEGF inhibitor).
For Renal Medullary Carcinoma (RMC) patients prior radiographic evidence of disease progression on/after at least one line of chemotherapy (e.g. carboplatin / paclitaxel, carboplatin / paclitaxel / bevacizumab, carboplatin / gemcitabine, and gemcitabine / doxorubicin).
No maximum lines of therapy
Both Cohorts 1 \& 2
Adequate Hematologic Function
Absolute Neutrophil Count ≥ 1.5 x 10\^9 / L
Platelet Count ≥ 100 x 10\^9 / L
Hemoglobin ≥ 9 g/dL
No transfusion of packed red blood cells or platelets within 21 days of Cycle 1 Day 1
Adequate Renal Function ≥ 30 ml/min according to the Cockcroft-Gault Equation
Patients with moderate renal impairment (creatinine clearance 30-59 by Cockcroft-Gault EquationI) will start with a reduced dose of talazoparib.
Adequate Hepatic Function including:
Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
AST ≤ 3 x upper limit of normal (ULN) without liver metastasis
ALT ≤ 3 x upper limit of normal (ULN) without liver metastasis
AST or ALT ≤ 5 x upper limit of normal (ULN) for patients with liver metastasis

You may not qualify if…

Patients < 18 years old
Patients who are pregnant or breast-feeding. Fertile patients who are unwilling or unable to use two methods of contraception (at least one of which considered highly effective) for duration of study and after 7 months after last dose of study treatment for female, and 4 months for males.
Patients who had prior immune checkpoint blockade therapy (either anti-PD-1, anti- PD-L1 and/or anti-CTLA-4) discontinued due to development of an immune related adverse event.
Prior diagnosis of myelodysplastic syndrome (MDS) or diagnosis of other malignancy that requires anti-cancer directed therapy within the last 24 months. Exclusions include those cancers that are considered cured by local therapy (i.e.Basal cell carcinoma, squamous cell carcinoma, ducal carcinoma in situ of breast, bladder of cervix) or other cancers that have low malignant potential and do not require systemic therapy (i.e. Gleason-grade <6 prostate adenocarcinoma, borderline ovarian malignancy / low malignant potential).
Prior treatment with talazoparib or other agents that target PARP
Treatment with anti-cancer therapies within 21 days or five half-lives, whichever shorter, of start date, including monoclonal antibody, cytotoxic therapy, or another investigational agent. There is no specific time window between last PD-1/PD-L1 therapy and start date of new therapy on protocol.
Significant vascular disease (i.e. aortic aneurysm requiring surgical repair, recent arterial thrombosis) within 6 months prior to first dose of therapy.
Evidence of bleeding diathesis or significant unexplained coagulopathy (i.e. absent of anticoagulation)
Clinical signs or symptoms of gastrointestinal obstruction requirement parenteral hydration, parenteral nutrition, or feeding tube.
Uncontrolled effusion management (pleural effusion, pericardial effusion, or ascites) which requires recurrent drainage procedures.
Patients treated with systemic immunosuppressants; except for
chronic physiologic replacement of ≤ 10mg prednisone (or equivalent) for treatment of adrenal insufficiency; Steroids required for pre-medication reactions
Local steroid use is permitted (e.g. intranasal, topical, inhaled, or local steroid injection, i.e. intra-articular)
Patients with autoimmune disease that may worsen during immune checkpoint blockade therapy are excluded. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requirement immunosuppressive treatment as above are eligible.
Prior organ transplantation including allogeneic stem cell transplant.
No active infection requiring parenteral antibiotic therapy.
Prior diagnosis of HIV/AIDS
History of either positive HCV RNA viral load or anti-HCV antibody screening detectable; HBV infection with HBV surface antigen detection and/or positive HBV DNA viral load.
Known hypersensitivity to talazoparib or avelumab, or any component in formulations. Patients with known hypersensitivity to monoclonal antibodies (Grade ≥3 by CTCAE v5.0)
Live vaccination within 4 weeks of first dose of therapy. All vaccines except inactivated are prohibited while on study.
Severe acute or chronic medical conditions which may significantly increase the risk of study participants, per treating investigator's discretion
Radiation therapy to any site (including bone) <2 weeks prior to the first dose of therapy. Patients with clinically relevant ongoing complications from prior radiation therapy, per investigators' assessment, are not eligible.
Symptomatic brain metastasis or leptomeningeal disease requiring steroid use. Patients are eligible if they neurologically stable for 4 weeks, and have completed radiation therapy or surgery, and recovered from side effects. Patients must have discontinued steroid therapy for at least 2 weeks prior to first dose of study treatment.
Current or anticipated use of potent P-gp inhibitors within 7 days prior to randomization or anticipated use during the study. Please see Appendix 5 for a list of potent P-gp inhibitors.
Inability to swallow capsules, known intolerance to talazoparib or its excipients, known malabsorption syndrome, or other conditions which impair intestinal absorption.

Where it is running

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States
Memorial Sloan Kettering Commack (Limited Protocol Activities) — Commack, New York, United States
Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison, New York, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States
Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States

Full record on ClinicalTrials.gov

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