MelanomaPhase 1/2NCT06683755
Phase I/IIa Dose Finding Study of Triplet Regimen of Relatlimab Ipilimumab and NIvolumab in First Line Therapy of Metastatic Melanoma (TRINITY)
A Phase 1/2 study testing Nivolumab, Relatlimab and Ipilimumab in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To determine the recommended Phase IIa dose (RP2D) of the triplet combination. To determine the safety and efficacy of the combination at the RP2D. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Nivolumab, Relatlimab and Ipilimumab
- 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
- 31 Dec 2024to 16 Aug 2032
- Phase
- Phase 1/2
- 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.
- ECOG performance status 0-1
- 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 unresectable stage III or stage IV malignant melanoma (Stage IV).
- At least one measurable target lesion according to RECIST 1.1. (Appendix 1), which previously was not treated.
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- 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
- Tumor tissue from an unresectable or metastatic site of disease must be available for biomarker analyses. The biopsy should be a core biopsy, a punch biopsy, an excisional biopsy, or a surgical specimen. Fine needle aspiration is unacceptable for submission
- For Phase I participants: Pretreatment tissue must be available through either an archival sample obtained within at most 6 months and submitted as an FFPE tissue block or 30 unstained tumor tissue slides or a fresh pretreatment biopsy. Subsequent tumor biopsies will be optional.
- For Phase IIa participants: Either an archival sample submitted as an FFPE tissue block or unstained tumor tissue slides or a fresh pretreatment biopsy from safely biopsiable lesion. Note that if the patient has archival tissue available from a biopsy within 90 days of C1D1 and there has been no systemic treatment since that time then that tissue can be used in place of a fresh pre-treatment biopsy. Patients must also agree to undergo post treatment, cycle 2, tumor biopsies for research purposes. Subsequent biopsies will be optional.
- No prior systemic lines of treatment for metastatic melanoma. Prior adjuvant or neo-adjuvant therapy will be permitted as long as it did not contain ipilimumab and the last dose has been >6 months.
- Prior radiation is allowed with a two week wash out period prior to initiation of treatment.
- Adequate organ function as described below.
- Table 2. Evaluation of Organ Function Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.5 X 109/L Platelets ≥ 100 X 109/L (≥ 60 for HCC) Hemoglobin ≥ 8.0 g/dL Renal Creatinine OR ≤1.5 × ULN OR Measured or calculatedb creatinine clearance ≥40 mL/min for participant with creatinine levels >1.5 × institutional (GFR can also be used in place of creatinine or ULN CRCl) Hepatic
- 1.5 ×ULN OR direct bilirubin ≤ULN Total bilirubin for participants with total bilirubin levels AST (SGOT) and ALT (SGPT) ≤3.0 × ULN (≤5 × ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR ≤1.5 × ULN unless participant is receiving prothrombin time (PTT) anticoagulant therapy as long as PT or Activated partial thromboplastin time aPTT wi withing therapeutic range of intended use of anticoagulants (aPTT) ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
- a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
- b Creatinine clearance (CrCl) should be calculated per institutional standard. NOTE: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
- 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 4. 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 low grade or non-serious toxicities. However, stable endocrinopathies requiring replacement therapy will be allowed.
- Steroids for physiological replacement are allowed as long as it does not exceed 10 mg/day prednisone equivalents.
- Participants must have known BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional standards during the screening period. BRAF V600 results need not be available at the time of study start.
- Participants with asymptomatic brain metastases are eligible. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 10 days prior to study treatment administration. Patients with brain metastases treated with SRS will be allowed, as long as last radiation therapy is >1 week.
Who cannot join
- Patients with ocular melanoma.
- Patients with symptomatic CNS metastases and/or requiring corticosteroid treatment.
- History of known leptomeningeal involvement (lumbar puncture not required).
- Patients who experienced Grade 3/4 immune-related adverse events with checkpoint inhibitor therapy, except those that are unlikely to re-occur with standard countermeasures (e.g. hypothyroidism)
- 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.
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- 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).
- History of hepatitis B or hepatitis C infection, defined as reactive hepatitis B surface antigen (HBsAg) or detectable hepatitis C virus (HCV) RNA by qualitative testing. Patients with reactive HBsAg are excluded unless HBV DNA is <500 IU/mL and the patient is receiving antiviral therapy.
- 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.
- 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 14 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 or in the case of Inhaled or topical steroids or other immunosuppressive medications. If alternative corticosteroid therapy has been used, consultation with the PI is required to determine the washout period prior to initiating study treatment.
- 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. Also, • prior myocarditis of any etiology. • Left ventricular ejection fraction (LVEF) assessment with documented LVEF < 50% by either transthoracic echocardiogram (TTE) or multigated acquisition scan (TTE preferred test) within 6 months prior to the start of study treatment.
- 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 shorter) of the first dose of the triplet therapy.
- The use of herbal supplements within 7 days.
- 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.
United States1 site, 1 recruiting
- Recruiting
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030
Hussein Tawbi, MD,PHD, 713-792-4185, htawbi@mdanderson.org
Hussein Tawbi, MD,PHD
About this study
To determine the recommended Phase IIa dose (RP2D) of the triplet combination.
To determine the safety and efficacy of the combination at the RP2D.
Read the detailed description
Primary Objectives:
Phase I:
Primary Objective of the Phase I portion is to determine the recommended Phase IIa dose (RP2D) of ipilimumab in combination with nivolumab and relatlimab in the first line treatment of patients with metastatic melanoma.
Phase IIa:
Primary Objective of the Phase IIa portion is to determine the preliminary clinical efficacy of ipilimumab at the RP2D in combination with nivolumab and relatlimab in the first line treatment of patients with metastatic melanoma as determined by overall response rate (ORR) according to RECIST 1.1.
Secondary Objectives:
- Phase I: To assess the overall response rates by RECIST 1.1 (as assessed by Investigator/site designated radiologist).
- Phase IIa: To determine the safety and tolerability of the triplet combination.
- To assess the progression free survival (PFS), and overall survival for patients treated with the triplet combination
- Assess the PFS and ORR to subsequent therapies in the second and third line setting.
- Evaluate the pharmacodynamic effects of the combination in tumor tissues obtained at baseline (archival and/or fresh tissue), on treatment, and at time of progression.
- Peripheral blood assays to assess for immunologic changes and immune cell subsets
- Conditions
- Melanoma
- Being tested
- Nivolumab, Relatlimab, Ipilimumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Given by IV
RelatlimabDrug
Given by IV
IpilimumabDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab | Experimental | Participants particiapting on study will be randomized Receives: Drug: Nivolumab; Drug: Relatlimab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse Events (AEs)
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 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2024
- Study start31 Dec 2024
- Primary completion16 Aug 2030 (estimated)
- Study completion16 Aug 2032 (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 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hussein Tawbi, MD,PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06683755
- Sponsor's protocol ID
- 2024-1032
- Other IDs
- NCI-2024-09421
- Status last verified
- Aug 2026
- First submitted
- 8 Nov 2024
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa Dose Finding Study of Triplet Regimen of Relatlimab Ipilimumab and NIvolumab in First Line Therapy of Metastatic Melanoma (TRINITY)
- ClinicalTrials.gov ID
- NCT06683755
- Acronym / sponsor ID
- 2024-1032
- Conditions
- Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 31 Dec 2024 (actual)
- Primary completion
- 16 Aug 2030 (estimated)
- Study completion
- 16 Aug 2032 (estimated)
- First posted
- 12 Nov 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.
To determine the recommended Phase IIa dose (RP2D) of the triplet combination.
To determine the safety and efficacy of the combination at the RP2D.
Detailed description
Primary Objectives:
Phase I:
Primary Objective of the Phase I portion is to determine the recommended Phase IIa dose (RP2D) of ipilimumab in combination with nivolumab and relatlimab in the first line treatment of patients with metastatic melanoma.
Phase IIa:
Primary Objective of the Phase IIa portion is to determine the preliminary clinical efficacy of ipilimumab at the RP2D in combination with nivolumab and relatlimab in the first line treatment of patients with metastatic melanoma as determined by overall response rate (ORR) according to RECIST 1.1.
Secondary Objectives:
- Phase I: To assess the overall response rates by RECIST 1.1 (as assessed by Investigator/site designated radiologist).
- Phase IIa: To determine the safety and tolerability of the triplet combination.
- To assess the progression free survival (PFS), and overall survival for patients treated with the triplet combination
- Assess the PFS and ORR to subsequent therapies in the second and third line setting.
- Evaluate the pharmacodynamic effects of the combination in tumor tissues obtained at baseline (archival and/or fresh tissue), on treatment, and at time of progression.
- Peripheral blood assays to assess for immunologic changes and immune cell subsets
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab | Experimental | Drug: Nivolumab, Drug: Relatlimab, Drug: IpilimumabParticipants particiapting on study will be randomized |
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.
- ECOG performance status 0-1
- 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 unresectable stage III or stage IV malignant melanoma (Stage IV).
- At least one measurable target lesion according to RECIST 1.1. (Appendix 1), which previously was not treated.
Key exclusion criteria (21 listed)
- Patients with ocular melanoma.
- Patients with symptomatic CNS metastases and/or requiring corticosteroid treatment.
- History of known leptomeningeal involvement (lumbar puncture not required).
- Patients who experienced Grade 3/4 immune-related adverse events with checkpoint inhibitor therapy, except those that are unlikely to re-occur with standard countermeasures (e.g. hypothyroidism)
- 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.
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 |
|---|---|---|
| NivolumabGiven by IV | Drug | Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab |
| RelatlimabGiven by IV | Drug | Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab |
| IpilimumabGiven by IV | Drug | Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab |
Primary outcome
Safety and Adverse 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
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 28 Aug 2026.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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 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 1/2 study testing Nivolumab, Relatlimab and Ipilimumab in people with Melanoma, 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 21 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 28 Aug 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year). 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 28 Aug 2026.