MelanomaPhase 2NCT06712927
Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases
A Phase 2 study testing Ipilimumab and Nivolumab + Relatlimab FDC in people with Melanoma and Brain Metastases, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Brain Metastases
- What is being tested?
- Ipilimumab and Nivolumab + Relatlimab FDC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2025to Feb 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- 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.
- 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:
Show all 25Show fewer
- 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.
- 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.
- Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable.
- However, if repeat biopsy is not feasible, and no archival tissue available patient still may be enrolled.
- 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).
- 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).
- 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
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Phuong Q Pham contact
United States1 site, 1 recruiting
- Recruiting
Stanford University
Palo Alto, California, 94304
Divya Divya Pathak, 650-492-3674, divya22@stanford.edu
Phuong Q Pham, ppham5@stanford.edu
About this study
Official title: A Multicenter, Phase II Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases
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
- Being tested
- Ipilimumab, Nivolumab + Relatlimab FDC
- Keywords
- Relatlimab, Nivolumab, Ipilimumab
- Medical subject headings
- Melanoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy
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
Nivolumab + Relatlimab FDCDrug
Also called Opdualag
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
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Asymptomatic | Experimental | Not described Receives: Drug: Ipilimumab; Drug: Nivolumab + Relatlimab FDC |
| Cohort B: Symptomatic | Experimental | Not described Receives: Drug: Ipilimumab; Drug: Nivolumab + Relatlimab FDC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (10)
Evaluation of Safety and Adverse Events Using CTCAE v5.0
Safety will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Measured: 6 months
Extracranial objective response rate
Extracranial objective response rate, defined as the percentage of patients who had a complete response (CR) or partial response (PR) per RECIST 1.1 criteria.
Measured: 6 months
Global objective response rate
Global objective response rate, defined as the percentage of patients who had a complete response (CR) or partial response (PR) per modified RECIST 1.1 criteria.
Measured: 6 months
Extracranial clinical benefit rate
Extracranial 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 RECIST 1.1 criteria.
Measured: 6 months
Global clinical benefit rate
Global 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.
Measured: 6 months
Duration of response
Duration of response, measured from time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or death.
Measured: 60 months
Progression-free survival
Progression-free survival, defined as the duration of time from start of treatment to time of progression or death.
Measured: 60 months
Intracranial progression-free survival
Intracranial progression-free survival, defined as the duration of time from start of treatment to time of intracranial progression or death.
Measured: 60 month
Overall survival
Overall survival, defined as the duration of time from the start of treatment to death.
Measured: 60 months
Intracranial Objective response rate
Intracranial objective response rate, defined as the percentage of patients who had a complete response (CR) or partial response (PR) per modified RECIST 1.1 criteria.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2024
- Study start6 Aug 2025
- Primary completionNov 2026 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Allison Betof, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06712927
- Sponsor's protocol ID
- IRB-78364
- Other IDs
- NCI-2025-09171
- Status last verified
- May 2026
- First submitted
- 27 Nov 2024
- Last updated
- 18 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Phase II Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases
- ClinicalTrials.gov ID
- NCT06712927
- Acronym / sponsor ID
- IRB-78364
- Conditions
- Melanoma, Brain Metastases
- Keywords
- Relatlimab, Nivolumab, Ipilimumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 6 Aug 2025 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 3 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, phase II trial of relatlimab (rela), nivolumab (nivo), and ipilimumab (ipi) in patients with asymptomatic and symptomatic melanoma brain metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Asymptomatic | Experimental | Drug: Ipilimumab, Drug: Nivolumab + Relatlimab FDC |
| Cohort B: Symptomatic | Experimental | Drug: Ipilimumab, Drug: Nivolumab + Relatlimab FDC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
- 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:
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabAlso: Yervoy1 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 | Cohort A: Asymptomatic, Cohort B: Symptomatic |
| Nivolumab + Relatlimab FDCAlso: OpdualagRelatlimab 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 | Drug | Cohort A: Asymptomatic, Cohort B: Symptomatic |
Primary outcome
Intracranial clinical benefit rate
Time frame: 6 months
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.
10 secondary outcomes
Evaluation of Safety and Adverse Events Using CTCAE v5.0
Time frame: 6 months
Extracranial objective response rate
Time frame: 6 months
Global objective response rate
Time frame: 6 months
Extracranial clinical benefit rate
Time frame: 6 months
Global clinical benefit rate
Time frame: 6 months
Duration of response
Time frame: 60 months
Progression-free survival
Time frame: 60 months
Intracranial progression-free survival
Time frame: 60 month
Overall survival
Time frame: 60 months
Intracranial Objective response rate
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2026.
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Phuong Q Pham contact
Allison Betof, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab and Nivolumab + Relatlimab FDC in people with Melanoma and Brain Metastases, run by Stanford University at 1 site 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 25 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Divya Pathak ((650) 492-3674, divya22@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracranial clinical benefit rate (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 May 2026.