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Metastatic Renal Cell CarcinomaPhase 2NCT04068831

Talazoparib and Avelumab in Participants With Metastatic Renal Cell Carcinoma

A Phase 2 study testing Talazoparib and Avelumab in people with Metastatic Renal Cell Carcinoma and Fumarate Hydratase Deficient Renal Cell Carcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Talazoparib and Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
7 sitesUnited States
Study dates
22 Aug 2019to 6 Dec 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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
  • Patients with known Gilbert's syndrome may be included if total bilirubin ≤ x 3 ULN
  • Eastern Cooperative Group (ECOG) Performance Status 0-2.
  • Patients must have measurable disease by RECIST v1.1. At least one measurable lesion should not have been previously irradiated.
  • Women of childbearing potential must have negative serum pregnancy testing at screening. All women will be considered childbearing potential unless meeting criteria including:
  • Achieved post-menopausal status as defined by cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have follicular stimulation hormone showing postmenopausal state. Women who have been amenorrhoeic for ≥12 months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anorexia, low body weight, ovarian suppression, anti-estrogen therapy or other medically inducible reasons.
  • Documented hysterectomy or bilateral oophorectomy surgery
  • Medically confirmed ovarian failure
  • Sexually active participants and their partners must agree to use medically accepted methods of contraception (i.e. barrier methods including condoms, female condom, or diaphragm with spermicidal gel) during the study and for 7 months after the last dose of the study treatment for females, and 4 months for males.
  • Recovery of baseline CTCAE v5.0 grade ≤1 toxicities related to prior study treatments unless adverse events are clinically non-significant and/or stable on supportive therapy if needed.
  • Patients must be willing and able to comply with trial protocol. This includes adhering to the treatment plan, scheduled visits, laboratory and other study procedures.

Who cannot join

  • 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.
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  • 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.
  • Investigator site staff members directly involved in study conduct, including but not limited to their family members, or patients who are Pfizer members, including their family members, who are directly involved in study conduct.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack (Limited Protocol Activities)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (All Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Talazoparib and Avelumab in Genomically Defined Metastatic Renal Cell Carcinoma

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.

Being tested
Talazoparib, Avelumab
Keywords
Talazoparib, Avelumab, 19-195
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TalazoparibDrug

    Also called BMN-673

    1 mg talazoparib daily

  • AvelumabDrug

    800 mg avelumab every 2 weeks

Study groups in NCT04068831
Study groupRoleWhat they receive
Talazoparib and Avelumab (VHL-deficiency) (Closed to Accrual)ExperimentalAll 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.
Receives: Drug: Talazoparib; Drug: Avelumab
Talazoparib and Avelumab (FH- or SDH-deficiency)ExperimentalAll 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.
Receives: Drug: Talazoparib; Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. the Objective Response Rate (ORR)

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

    Measured: 4 months

Secondary outcomes (1)

  1. Progression-free Survival (PFS)

    by RECIST v1.1

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2019
  2. Study start22 Aug 2019
  3. Primary completion6 Dec 2023
  4. Study completion6 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04068831
Sponsor's protocol ID
19-195
Status last verified
Dec 2024
First submitted
23 Aug 2019
Last updated
27 Dec 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Talazoparib and Avelumab in people with Metastatic Renal Cell Carcinoma and Fumarate Hydratase Deficient Renal Cell Carcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the Objective Response Rate (ORR) (time frame: 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04068831.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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