Talazoparib and Avelumab in Participants With Metastatic Renal Cell Carcinoma

NCT04068831 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 19-195
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Metastatic Renal Cell Carcinoma; Fumarate Hydratase Deficient Renal Cell Carcinoma; Succinate Dehydrogenase Deficient Renal Cell Carcinoma

Keywords

Talazoparib; Avelumab; 19-195

Outcome Measures

Primary Outcomes (1)

• the Objective Response Rate (ORR)

  confirmed complete response (iCR) or partial response (iPR) assessed by iRECIST.

  4 months

Secondary Outcomes (1)

• Progression-free Survival (PFS)

  2 years

Study Arms (2)

Talazoparib and Avelumab (VHL-deficiency) (Closed to Accrual)

EXPERIMENTAL

All patients will receive combination treatment at the previously established recommended phase II dose, 800 mg avelumab every 2 weeks with 1 mg talazoparib daily, in 28-day cycles.

Drug: Talazoparib; Drug: Avelumab

Talazoparib and Avelumab (FH- or SDH-deficiency)

EXPERIMENTAL

All patients will receive combination treatment at the previously established recommended phase II dose, 800 mg avelumab every 2 weeks with 1 mg talazoparib daily, in 28-day cycles.

Drug: Talazoparib; Drug: Avelumab

Interventions

Talazoparib DRUG

1 mg talazoparib daily

Also known as: BMN-673

Talazoparib and Avelumab (FH- or SDH-deficiency); Talazoparib and Avelumab (VHL-deficiency) (Closed to Accrual)

Avelumab DRUG

800 mg avelumab every 2 weeks

Talazoparib and Avelumab (FH- or SDH-deficiency); Talazoparib and Avelumab (VHL-deficiency) (Closed to Accrual)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

talazoparib; avelumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Ritesh Kotecha, MD
• Organization: Memorial Sloan Kettering Cancer Center

kotechar@mskcc.org

646-422-4791

Study Officials

• Ritesh Kotecha, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase II, open-label, single-institution trial.This is a phase II, open-label, single institution clinical trial of combination talazoparib and avelumab in patients with metastatic RCC. This clinical trial will enroll two separate cohorts in parallel.

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: August 28, 2019
• Study Start: August 22, 2019
• Primary Completion: December 6, 2023
• Study Completion: December 6, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF

Locations

US (7)