Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases

NCT06712927 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: IRB-78364NCI-2025-09171
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, phase II trial of relatlimab (rela), nivolumab (nivo), and ipilimumab (ipi) in patients with asymptomatic and symptomatic melanoma brain metastases.

Conditions

Melanoma; Brain Metastases

Keywords

Relatlimab; Nivolumab; Ipilimumab

Outcome Measures

Primary Outcomes (1)

• Intracranial clinical benefit rate

  Intracranial clinical benefit rate, defined as the percentage of patients who had a complete response (CR), partial response (PR), or stable disease for at least 6 months per modified RECIST 1.1 criteria.

  6 months

Secondary Outcomes (10)

• Evaluation of Safety and Adverse Events Using CTCAE v5.0

  6 months

• Extracranial objective response rate

  6 months

• Global objective response rate

  6 months

• Extracranial clinical benefit rate

  6 months

• Global clinical benefit rate

  6 months

Study Arms (2)

Cohort A: Asymptomatic

EXPERIMENTAL

Drug: Ipilimumab; Drug: Nivolumab + Relatlimab FDC

Cohort B: Symptomatic

EXPERIMENTAL

Drug: Ipilimumab; Drug: Nivolumab + Relatlimab FDC

Interventions

Ipilimumab DRUG

1 mg/kg of Ipilimumab will be administered via IV every 8 weeks. Participants will be assigned to Cohort A or B as per eligibility criteria. No randomization or blinding will occur

Also known as: Yervoy

Cohort A: Asymptomatic; Cohort B: Symptomatic

Nivolumab + Relatlimab FDC DRUG

Relatlimab 160mg + Nivo 480mg will be administered via IV every 4 weeks. Participants will be assigned to Cohort A or B as per eligibility criteria. No randomization or blinding will occur

Also known as: Opdualag

Cohort A: Asymptomatic; Cohort B: Symptomatic

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed non-uveal melanoma that has metastasized to the brain. At least 1 measurable intracranial target lesion (5-40mm) which was not previously treated with local therapy (no prior SRS to this lesion). Prior surgery for a brain metastasis is allowed but this lesion cannot be a target lesion.
• a. Growth or change in a lesion previously irradiated will not be considered measurable. Regrowth in cavity of previously excised lesion will not be considered measurable.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 for Cohort A (asymptomatic), ECOG performance status 0-2 for Cohort B (symptomatic)
• No prior anti-CTLA-4, anti-PD-1, or anti-LAG-3 therapy for unresectable stage III/IV melanoma. Prior CTLA-4, PD-1, and/or LAG-3 therapy in the neoadjuvant or adjuvant setting is acceptable if \>6 months since last treatment. Participants may have had prior BRAF+MEK inhibitors for adjuvant therapy and/or unresectable/metastatic melanoma if \>2 weeks have elapsed since last treatment.
• Adequate organ function as assessed by the following parameters:
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (≤ 3 ×ULN); patients with liver metastasis ≤ 5 × ULN
• Estimated creatinine clearance (eCrCl) ≥ 30 mL/min using the Cockcroft-Gault formula at Screening
• Total bilirubin ≤ 1.5x ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5x ULN
• Patients must have recovered from all prior anti-cancer therapy-related adverse events (AEs) to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] v 5.0), except for alopecia, vitiligo, thyroid dysfunction, hypophysitis, or adrenal insufficiency, prior to enrollment.
• Cohort A (asymptomatic): participants must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy greater than physiologic replacement (\>10 mg of prednisone/day or equivalent) in the 10 days prior to beginning protocol therapy. Cohort B (symptomatic): participants may be on steroids with doses no higher than a total daily dose of 4 mg of dexamethasone or equivalent that is stable or tapering within 10 days prior to treatment. Patients who are symptomatic and are not being treated with steroids are also eligible.
• Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to treatment.
• Participants with a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection must have been treated and cured. Participants with HBV or HCV infection who are currently on treatment must have an undetectable HCV viral load prior to treatment.
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) OR at least 4 unstained slides, with an associated pathology report, for testing of tumor PD-L1 expression:
• Tumor tissue should be of good quality based on total and viable tumor content.

You may not qualify if:

• Another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated).
• Active medical illness(es) that would pose increased risk for study participation, including: active systemic infections (including COVID-19), coagulation disorders, or other major active medical illnesses of the cardiovascular, respiratory, or immune systems.
• Active autoimmune disease that has required systemic therapy with corticosteroids or other immunosuppressive agents within the past 3 years (excluding immune-related adverse events from immunotherapy as described above.
• Implanted device that precludes the use of MRI.
• Prior Grade 4 treatment-related AE with immune checkpoint inhibitor treatment.
• History of leptomeningeal metastasis determined by imaging or lumbar puncture.
• Prior whole brain radiation therapy (WBRT)
• Women who are breast-feeding or pregnant
• History of clinically significant cardiac disease or congestive heart failure \> New York Heart Association (NYHA) class 2. Subjects must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months or a history of myocarditis
• Troponin T (TnT) or I (TnI) \> 2 × institutional 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 consultation and be considered for treatment, following cardiologist recommendation. 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 consultation and be considered for treatment, following cardiologist recommendation. Notification of the decision to enroll the participant following cardiologist recommendation has to be made to the principal investigator.
• Investigational drug use within 14 days (or 5 half-lives, whichever is longer) of the first dose of study treatment.
• Dexamethasone use \> 4mg/day (or equivalent)

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

Ipilimumab; Nivolumab; Opdualag

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Allison Betof, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Divya Pathak

CONTACT

(650) 492-3674; divya22@stanford.edu

Phuong Q Pham

CONTACT

ppham5@stanford.edu

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

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 3, 2024
• Study Start: August 6, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): February 1, 2030
• Last Updated: May 18, 2026

Record last verified: 2026-05

Locations

US (1)