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

A Multicenter, Phase II Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases

Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases (NCT06712927) is a Phase 2 interventional studying Melanoma and Brain Metastases, sponsored by Stanford University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Melanoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 60 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Melanoma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. diagnosed by tissue sample (biopsy-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. 2. Age ≥ 18 years 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 for Cohort A (asymptomatic), You should be able to carry out daily activities with 0 level of ability (ECOG 0)-2 for Cohort B (symptomatic) 4. 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. 5. your organs (liver, kidneys, etc.) are working well enough based on blood tests as assessed by the following parameters: 1. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (≤ 3 ×ULN); patients with liver metastasis ≤ 5 × ULN 2. Estimated creatinine clearance (eCrCl) ≥ 30 mL/min using the Cockcroft-Gault formula at Screening 3. Total bilirubin ≤ 1.5x ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5x ULN 6. 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. 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. 2. Age ≥ 18 years 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 for Cohort A (asymptomatic), ECOG performance status 0-2 for Cohort B (symptomatic) 4. 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. 5. Adequate organ function as assessed by the following parameters: 1. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (≤ 3 ×ULN); patients with liver metastasis ≤ 5 × ULN 2. Estimated creatinine clearance (eCrCl) ≥ 30 mL/min using the Cockcroft-Gault formula at Screening 3. Total bilirubin ≤ 1.5x ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5x ULN 6. 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. 7. 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. 8. 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. 9. 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. 10. 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: 1. Tumor tissue should be of good quality based on total and viable tumor content. 2. Patients who do not have tissue specimens may undergo a biopsy during the screening period. Acceptable samples include core-needle biopsies for deep tumor tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Fine Needle Aspirations (FNA) will not be considered acceptable for tissue procurement. 3. Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable. 4. However, if repeat biopsy is not feasible, and no archival tissue available patient still may be enrolled. 11. Any radiation treatment or excision of non-target brain lesions must have occurred ≥ 1 weeks before the start of dosing for this study. NOTE: The radiation field must not have included the brain index lesion(s). 12. Radiation to non-CNS lesions is allowed and does not require a washout period for treatment initiation. Any radiation-related toxicity must have recovered to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] v 5.0). 13. Women of child-bearing potential (WOCBP) must not be breastfeeding and must have a negative pregnancy test within 3 days prior to initiation of dosing. WOCBP (or female partners of male participants) must agree to use an acceptable method of birth control from the time of the negative pregnancy test, through the duration of treatment with the study combination and for 12 months after their last dose of any study component medication. NOTE: A female participant is eligible to participate if she is not a woman of childbearing potential. Approved methods of birth control are as follows: Combined (estrogen and progesterone containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal Progesterone-only hormonal birth control associated with inhibition of ovulation: oral, injectable, implantable Intrauterine device (IUD) Intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Vasectomized partner True sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) is not acceptable 14. Patients (or legally authorized representative) must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC) and agree to abide by the study restrictions and return to the site for the required assessments. Exclusion Criteria 1. 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). 2. 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. 3. 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. 4. Implanted device that precludes the use of MRI. 5. Prior Grade 4 treatment-related AE with immune checkpoint inhibitor treatment. 6. History of leptomeningeal metastasis determined by imaging or lumbar puncture. 7. Prior whole brain radiation therapy (WBRT) 8. Women who are breast-feeding or pregnant 9. 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 10. 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. 11. Investigational drug use within 14 days (or 5 half-lives, whichever is longer) of the first dose of study treatment. 12. Dexamethasone use \> 4mg/day (or equivalent)

Treatments Being Tested

DRUG

Ipilimumab

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

DRUG

Nivolumab + Relatlimab FDC

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

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Stanford University

Palo Alto, California, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06712927), the sponsor (Stanford University), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06712927 clinical trial studying?

This is a multicenter, phase II trial of relatlimab (rela), nivolumab (nivo), and ipilimumab (ipi) in patients with asymptomatic and symptomatic melanoma brain metastases. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06712927?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06712927?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06712927. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06712927. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.