Melanoma (Skin)Phase 2NCT05704647

Phase II Study of Nivolumab in Combination With Relatlimab in Patients With Active Melanoma Brain Metastases

A Phase 2 study testing BMS-986213 (Relatlimab-Nivolumab FDC), Nivolumab and Relatlimab in people with Melanoma (Skin), run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

To learn if giving nivolumab in combination with relatlimab can help to control melanoma that has spread to the brain (melanoma with brain metastases). The safety and side effects of the study drug combination will also be studied. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Melanoma (Skin)
What is being tested?: BMS-986213 (Relatlimab-Nivolumab FDC), Nivolumab and Relatlimab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteUnited States
Study dates: 23 Feb 2023to 31 Jul 2028
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

Age ≥ 18 years old.
Life Expectancy > 12 weeks.
Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
Histologically confirmed malignant melanoma with measurable metastases in the brain (≥ 0.5 cm).
At least one measurable intracranial target lesion, which previously was not treated with local therapy (no prior SRS to this lesion).

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Largest diameter of ≥ 0.5cm, but ≤ 3cm as determined by contrast-enhanced MRI.
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.
Prior SRT and prior excision of up to 5 MBM is permitted if there has been complete recovery, with no neurologic sequelae, and measurable non irradiated lesions remain.
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.
Any prior SRT to brain lesions or prior excision must have occurred ≥ 1 weeks before the start of dosing for this study.
Radiation to NON-CNS lesions. Prior radiation to NON-CNS is allowed and does not require a washout period for treatment initiation.
Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy in the 5 days prior to beginning protocol therapy.
ECOG performance status ≤1.
Adequate organ function as described below.
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. She 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 plus 5 half lives of study treatment for a total of 5 months post -treatment completion. WOCBP must agree to adhere to the contraceptive guidance in Appendix 5. NOTE: A female participant is eligible to participate if she is not a woman of childbearing potential as defined Appendix 4.
All associated toxicity from previous or concurrent cancer therapy must be resolved (to ≤ grade 1 or baseline) prior to study treatment administration. This excludes non-serious toxicities. However, stable endocrinopathies requiring replacement therapy will be allowed.
Steroids for physiological replacement are allowed.

Who cannot join

History of known leptomeningeal involvement (lumbar puncture not required).
Previous stereotactic or highly conformal radiotherapy within 1 weeks before the start of dosing for this study. NOTE: The stereotactic radiotherapy field must not have included the brain index lesion(s).
Subjects previously treated with SRT > 5 lesions in the brain. Prior whole brain radiation is not allowed.
Brain lesion size > 3 cm.
Prior checkpoint inhibitor therapy in the metastatic setting
Patients who received ipilimumab and/or anti-PD1 as adjuvant or neoadjuvant therapy must have a 6-month washout before receiving any dosing on this study.

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Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.
Subject has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful treatment of superficial bladder cancer, in situ cervical cancer, or other in-situ cancers. Subjects with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
Skin Cancer Exclusion: Please note that basal cell carcinoma and squamous cell carcinoma is exempt from needing resection prior to treatment. (Resection can be completed after the start of treatment).
Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected).
NOTE: Without known history, testing needs to be performed to determine eligibility. Hepatitis C antibody (Ab) testing is allowed for screening purposes in countries where HCV RNA is not part of standard of care.
Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
The use of corticosteroids is not allowed for 10 days prior to initiation of therapy (based upon 5 times the expected half-life of dexamethasone) except patients who are taking steroids for physiological replacement. If alternative corticosteroid therapy has been used, consultation with the PI is required to determine the washout period prior to initiating study treatment.
Subjects with a condition requiring systemic treatment with either corticosteroids (≤ 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study initiation. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug (unless the wound has healed) or anticipation of the need for major surgery during the study.
Non-healing wound, ulcer, or bone fracture.
Women who are breast-feeding or pregnant.
Uncontrolled intercurrent illness (i.e., active infection ≥ grade 2) or concurrent condition that, in the opinion of the Investigator, would interfere with the study endpoints or the subject's ability to participate.
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 nivolumab and relatlimab.
With a history of non-infectious pneumonitis that required steroids or current pneumonitis.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Hussein Tawbi, MD,PHD contact

(713) 792-4185

htawbi@mdanderson.org

United States1 site, 1 recruiting

M D Anderson Cancer Center
Houston, Texas, 77030
Hussein Tawbi, MD,PHD, 713-792-4185, htawbi@mdanderson.org
Hussein Tawbi, MD,PHD
Recruiting

Other trials in United States

About this study

Read the detailed description

Primary Objectives:

To assess the intracranial objective response rate (iORR), defined as intracranial CR + PR per modified RECIST 1.1 criteria, of nivolumab + relatlimab (nivo+rela) in subjects with MBM and treatment naïve to anti-PD-1 agents in the metastatic setting.

Secondary Objectives:

To determine the safety of the combination of nivo+rela
To assess the clinical benefit rate (CBR), defined as CR + PR + SD >6 months, of the combination
To determine overall response rates (intracranial + extracranial), DoR, PFS, and using a modified version of iRANO and compared to modified RECIST v1.1 and Response Assessment in Neuro-oncology - Brain Metastases (RANO-BM) for patients treated with nivo+rela
To determine the 1-year intracranial progression-free survival rate for the combination of nivo+rela
To determine overall survival
Advanced MRI imaging to assess for edema, tumor response, and predictors of response and radiation necrosis
To evaluate the brain-specific safety and tolerability of the combination regimen in subjects with or without SRT received prior to study entry, or on study
To evaluate changes in neurocognitive function and health-related quality of life
To assess available tumor tissue - intracranial and/or extra cranial - in specimens obtained at baseline (archival and/or fresh tissue), on treatment, and at time of progression
To assess immune cell subsets by flow cytometry, TCR NGS for diversity and clonality, cytokine expression, cfDNA from peripheral blood.

Exploratory Endpoints:

Radiotherapy-assisted PFS defined as time from study treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 modified by excluding ≤ 5 lesions that can be treated by SRT from the sum of largest diameters from baseline onwards.
To explore the association between baseline and on-treatment gut microbiome features with response and toxicity
To understand the association between habitual diet and gut microbiome features in this study population.
To explore predictors of biological response through the change in metabolic parameters

Conditions: Melanoma (Skin)
Being tested: BMS-986213 (Relatlimab-Nivolumab FDC), Nivolumab, Relatlimab
Medical subject headings: Melanoma

What participants receive

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

BMS-986213 (Relatlimab-Nivolumab FDC)Drug
Also called Relatlimab, BMS-986016
Given by IV (vein)
NivolumabDrug
Given by IV (vein)
RelatlimabDrug
Given by IV (vein)

Study groups in NCT05704647
Study group	Role	What they receive
Relatlimab+Nivolumab	Experimental	Participants will receive nivolumab in combination with relatlimab by vein over about 30 minutes on Day 1 of each 28-day study cycle. You may receive up to 25 doses of the study drugs. Receives: Drug: BMS-986213 (Relatlimab-Nivolumab FDC); Drug: Nivolumab; Drug: Relatlimab

What is being measured

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

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: through study completion; an average of 2 years

Timeline

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

23 Feb 202331 Jul 2028

First posted30 Jan 2023
Study start23 Feb 2023
Primary completion31 Jul 2028 (estimated)
Study completion31 Jul 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05704647
Sponsor's protocol ID: 2021-1203
Other IDs: NCI-2023-00571
Status last verified: Jul 2026
First submitted: 19 Jan 2023
Last updated: 16 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Interested in taking part?

Hussein Tawbi, MD,PHD

(713) 792-4185

htawbi@mdanderson.org

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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All Melanoma (Skin) trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Study of Nivolumab in Combination With Relatlimab in Patients With Active Melanoma Brain Metastases
ClinicalTrials.gov ID: NCT05704647
Acronym / sponsor ID: 2021-1203
Conditions: Melanoma (Skin)
Phase: Phase 2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 30 participants (estimated)
Lead sponsor: M.D. Anderson Cancer CenterUniversity, hospital or other
Study start: 23 Feb 2023 (actual)
Primary completion: 31 Jul 2028 (estimated)
Study completion: 31 Jul 2028 (estimated)
First posted: 30 Jan 2023 (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.

Detailed description

Primary Objectives:

To assess the intracranial objective response rate (iORR), defined as intracranial CR + PR per modified RECIST 1.1 criteria, of nivolumab + relatlimab (nivo+rela) in subjects with MBM and treatment naïve to anti-PD-1 agents in the metastatic setting.

Secondary Objectives:

To determine the safety of the combination of nivo+rela
To assess the clinical benefit rate (CBR), defined as CR + PR + SD >6 months, of the combination
To determine overall response rates (intracranial + extracranial), DoR, PFS, and using a modified version of iRANO and compared to modified RECIST v1.1 and Response Assessment in Neuro-oncology - Brain Metastases (RANO-BM) for patients treated with nivo+rela
To determine the 1-year intracranial progression-free survival rate for the combination of nivo+rela
To determine overall survival
Advanced MRI imaging to assess for edema, tumor response, and predictors of response and radiation necrosis
To evaluate the brain-specific safety and tolerability of the combination regimen in subjects with or without SRT received prior to study entry, or on study
To evaluate changes in neurocognitive function and health-related quality of life
To assess available tumor tissue - intracranial and/or extra cranial - in specimens obtained at baseline (archival and/or fresh tissue), on treatment, and at time of progression
To assess immune cell subsets by flow cytometry, TCR NGS for diversity and clonality, cytokine expression, cfDNA from peripheral blood.

Exploratory Endpoints:

Radiotherapy-assisted PFS defined as time from study treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 modified by excluding ≤ 5 lesions that can be treated by SRT from the sum of largest diameters from baseline onwards.
To explore the association between baseline and on-treatment gut microbiome features with response and toxicity
To understand the association between habitual diet and gut microbiome features in this study population.
To explore predictors of biological response through the change in metabolic parameters

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Relatlimab+Nivolumab	Experimental	Drug: BMS-986213 (Relatlimab-Nivolumab FDC), Drug: Nivolumab, Drug: RelatlimabParticipants will receive nivolumab in combination with relatlimab by vein over about 30 minutes on Day 1 of each 28-day study cycle. You may receive up to 25 doses of the study drugs.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Age ≥ 18 years old.
Life Expectancy > 12 weeks.
Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
Histologically confirmed malignant melanoma with measurable metastases in the brain (≥ 0.5 cm).
At least one measurable intracranial target lesion, which previously was not treated with local therapy (no prior SRS to this lesion).

Key exclusion criteria (23 listed)

History of known leptomeningeal involvement (lumbar puncture not required).
Previous stereotactic or highly conformal radiotherapy within 1 weeks before the start of dosing for this study. NOTE: The stereotactic radiotherapy field must not have included the brain index lesion(s).
Subjects previously treated with SRT > 5 lesions in the brain. Prior whole brain radiation is not allowed.
Brain lesion size > 3 cm.
Prior checkpoint inhibitor therapy in the metastatic setting

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
BMS-986213 (Relatlimab-Nivolumab FDC)Also: Relatlimab, BMS-986016Given by IV (vein)	Drug	Relatlimab+Nivolumab
NivolumabGiven by IV (vein)	Drug	Relatlimab+Nivolumab
RelatlimabGiven by IV (vein)	Drug	Relatlimab+Nivolumab

Primary outcome

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: through study completion; an average of 2 years

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 16 Jul 2026.
M D Anderson Cancer CenterLink provided by the sponsor.

Related trials for Melanoma (Skin)

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Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
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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.

Hussein Tawbi, MD,PHD contact

(713) 792-4185

htawbi@mdanderson.org

Hussein Tawbi, MD, PHD principal investigator

M.D. Anderson Cancer Center

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 BMS-986213 (Relatlimab-Nivolumab FDC), Nivolumab and Relatlimab in people with Melanoma (Skin), run by M.D. Anderson Cancer Center 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 22 inclusion and 23 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 16 Jul 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 Hussein Tawbi, MD,PHD ((713) 792-4185, htawbi@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 2 years). 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 NCT05704647.

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 16 Jul 2026.