A Randomized Phase 2 Trial of Nivolumab, Relatlimab Plus Ipilimumab vs. Nivolumab Plus Ipilimumab in First-line Advanced Renal Cell Carcinoma (RCC)

May 12, 2026 updated by: M.D. Anderson Cancer Center
This is a phase 2 stratified, randomized, multicenter, study investigating the efficacy of a triplet arm treating with nivolumab 480 mg every 4 weeks (Q4W), relatlimab 160 mg Q4W and ipilimumab 1 mg/kg every 8 weeks (Q8W) intravenous (IV) versus a doublet arm treating with nivolumab 480 mg Q3W and ipilimumab 1mg/kg Q3W IV in first-line advanced RCC.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary Objectives:

To determine the safety and tolerability of nivolumab, relatlimab and ipilimumab in patients with untreated advanced RCC

• To assess the ORR of nivolumab, relatlimab and ipilimumab in patients with untreated advanced RCC

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Principal Investigator:
          • David McDermott, MD
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Michael Harrison, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Penn Medicine Abramson Cancer Center
        • Contact:
        • Principal Investigator:
          • Lin Mei, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
        • Principal Investigator:
          • Brian Rini, MD
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
        • Principal Investigator:
          • Hans Hammers, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas M. D. Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Eric Jonasch, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Willing and able to provide a signed and dated written informed consent.
  2. ≥ 18 years of age
  3. Confirmed diagnosis of RCC with a clear cell component
  4. Stage IV metastatic renal cell carcinoma per American Joint Committee on Cancer
  5. No prior systemic therapy for RCC. Prior neo/adjuvant systemic therapy is not allowed.
  6. Karnofsky performance status ≥ 70%.

  7. At least one measurable lesion as defined by RECIST 1.1 (Appendix 3)

    • A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion

  8. Adequate organ function within 28 days prior to first dose of protocol-indicated treatment, including:

    • White blood cell (WBC) ≥ 2,000 /µL
    • Absolute neutrophil count (ANC) ≥ 1,500/µL
    • Platelets ≥ 100,000/µL
    • Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance > 30 mL/min (measured or calculated by Cockroft-Gault formula)
    • Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who must have total bilirubin < 3.0 mg/dL)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
  9. Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug

  10. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment. An extension up to 72 hours prior to the start of study treatment is permissible in situations where results cannot be obtained within the standard 24-hour window.

    • "Women of childbearing potential" (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal.
    • Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes.
    • If menopausal status is considered for the purpose of evaluating childbearing potential, women < 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential.
  11. Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception Appendix 5 from the time of signing consent, and for 23 weeks after their last dose of protocol-indicated treatment.

Exclusion Criteria:

  1. Prior systemic treatment for RCC of any type including neoadjuvant or adjuvant therapy is not allowed.

  2. ≤ 28 days before first dose of protocol-indicated treatment:

    • Major surgery requiring general anesthesia.

  3. ≤ 14 days before first dose of protocol-indicated treatment:

    • Radiosurgery or radiotherapy
    • Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery)
    • Active infection requiring infusion treatment.
  4. Any history of or current CNS metastases

  5. Any condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment.

    • In the absence of active autoimmune disease, subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhalational) ≤ 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids ≤ 10 mg/day prednisone or equivalent daily (e.g. hormone replacement therapy needed in patients with hypophysitis)

  6. Active, known or suspected autoimmune disease (see Appendix 1 for a comprehensive list of autoimmune diseases and immune deficiencies).

    • Subjects with type I diabetes mellitus; endocrine organ dysfunction (e.g., hypothyroidism) that are controlled and only requiring only hormone replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring systemic treatment; or conditions not expected by the investigator to recur in the absence of an external trigger are permitted to enroll.

  7. Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements.
  8. History of myocarditis, regardless of etiology

  9. Troponin T (TnT) or I (TnI) > 2× institutional upper limit of normal (ULN)

    • Participants with TnT or TnI levels between > 1× to 2× ULN will be permitted if repeat levels within 24 hours are ≤ 1× ULN. If TnT or TnI levels are between > 1× to 2× ULN within 24 hours, the participant may undergo a cardiac evaluation and be considered for treatment, based on a favorable benefit/risk assessment by the Investigator.

    When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2× ULN, the participant may undergo a cardiac evaluation and be considered for treatment, based on a favorable benefit/risk assessment by the Investigator.

  10. Treatment with any live/attenuated vaccine within 30 days of first study treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment with Nivolumab + Ipilimumab
Participants will randonmized to study and treatment will be administered on an outpatient basis.
Drug: Drugs Nivolumab
Given by IV Infusion
Drug: Ipilimumab
Given by IV Infusion
Experimental: Treatment with Nivolumab + Relatlimab + Ipilimumab
Participants will randonmized to study and treatment will be administered on an outpatient basis.
Drug: Ipilimumab
Given by IV Infusion
Drug: BMS-986213 (Relatlimab-Nivolumab FDC)
Given by IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Averse events (AEs)
Time Frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Through study completion; an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Eric Jonasch, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2025

Primary Completion (Estimated)

December 15, 2026

Study Completion (Estimated)

December 15, 2028

Study Registration Dates

First Submitted

November 25, 2024

First Submitted That Met QC Criteria

November 25, 2024

First Posted (Actual)

November 29, 2024

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-1337
  • NCI-2025-01553 (Other Identifier: Clinical Trials Reporting Program (CTR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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