Sponsor: Regeneron Pharmaceuticals (industry)
Phase: 3
Start date: Sept. 9, 2024
Planned enrollment: 560
Fianlimab (REGN3767) is an investigational, fully human monoclonal antibody targeting LAG-3 being developed primarily in combination with the PD‑1 inhibitor cemiplimab for melanoma and other solid tumors. Multiple phase 3 trials are ongoing in advanced and adjuvant melanoma and in first-line non–small cell lung cancer (NSCLC); no phase 3 efficacy results have been reported as of October 7, 2025. (ascopubs.org)
Advanced melanoma (phase 1, multicohort; fianlimab 1600 mg Q3W + cemiplimab 350 mg Q3W) - PD‑1–naïve advanced disease: ORR 63% in two independent cohorts (n=40 each); combined across three cohorts without prior anti‑PD‑1 for advanced disease (n=98), ORR 61.2% with median PFS 13.3 months (95% CI, 7.5–NE). CR rates were 12–15% across PD‑1–naïve cohorts. (ascopubs.org) - Prior anti‑PD‑1 in the adjuvant setting (relapse after adjuvant therapy; n=13 within a cohort of n=18): ORR 61.5% and median PFS 12 months (95% CI, 1.4–NE). (ascopubs.org) - Prior anti‑PD‑1 for advanced disease (n=15): ORR 13.3% and median PFS 1.5 months (95% CI, 1.3–7.7). (ascopubs.org) - Post hoc/independent review updates: In a combined analysis of PD‑1–naïve cohorts (n=98) with longer follow‑up, ORR 57% by BICR (CR 25%, PR 33%) was reported, with activity observed irrespective of baseline LAG‑3 or PD‑L1 expression. (onclive.com)
Ongoing phase 3 melanoma trials (no results yet) - First‑line unresectable/metastatic melanoma: fianlimab + cemiplimab versus pembrolizumab; primary endpoint PFS; estimated sample size ~1,500+. (ascopubs.org) - Adjuvant high‑risk resected melanoma: fianlimab + cemiplimab versus pembrolizumab (double‑blind, three‑arm design). (ascopubs.org) - Additional phase 3 head‑to‑head versus relatlimab+nivolumab is enrolling. (yalemedicine.org)
NSCLC (ongoing; no results yet) - Two randomized phase 2/3 trials: (1) PD‑L1 ≥50% tumors—fianlimab + cemiplimab versus cemiplimab; (2) all‑comers with chemotherapy—fianlimab + cemiplimab + chemotherapy versus cemiplimab + chemotherapy. (ascopubs.org)
Across the melanoma phase 1 cohorts of fianlimab + cemiplimab: - Grade ≥3 treatment‑emergent AEs occurred in 44% of patients; grade ≥3 treatment‑related AEs in 22%. An increased incidence of adrenal insufficiency was noted (any‑grade 12%, grade 3–4 4%) relative to typical PD‑1 monotherapy experience; otherwise, the safety profile was broadly comparable to PD‑1 inhibitors. Common AEs included fatigue and rash. (ascopubs.org)
Notes: Efficacy figures above derive from early‑phase studies; confirmatory phase 3 outcomes are pending as of October 7, 2025. (ascopubs.org)
Last updated: Oct 2025
Goal: Compare the efficacy and safety of fixed-dose fianlimab plus cemiplimab versus the approved relatlimab plus nivolumab combination (Opdualag) as first-line therapy for unresectable stage III or stage IV melanoma. Additional goals include characterization of pharmacokinetics and immunogenicity of the investigational agents and detailed safety profiling, including immune-mediated toxicity.
Patients: Adults with histologically confirmed unresectable stage III or metastatic (stage IV) cutaneous melanoma, treatment-naive in the advanced setting, with measurable disease per RECIST 1.1, ECOG 0–1, adequate organ function, and known or testable BRAF V600 status. Key exclusions include uveal, acral, or mucosal melanoma; active/untreated brain metastases or spinal cord compression; significant autoimmune disease requiring systemic immunosuppression; prior checkpoint inhibitor therapy other than anti–PD-1/PD-L1 per protocol; uncontrolled HIV/HBV/HCV infection; history of myocarditis; and elevated baseline troponin >2× ULN.
Design: Multicenter, randomized, active-controlled, parallel-group phase 3 trial with 1:1 allocation to fianlimab plus cemiplimab or relatlimab plus nivolumab. Blinded independent central review is used for tumor assessments by RECIST 1.1. Planned enrollment is 560 participants.
Treatments: Experimental arm: fixed-dose fianlimab plus cemiplimab. Fianlimab is a fully human IgG4 monoclonal antibody targeting LAG-3, blocking its interaction with MHC class II to release inhibitory signaling on activated T cells and enhance antitumor immunity. In phase 1 melanoma studies combined with the anti–PD-1 antibody cemiplimab, objective response rates around 61% and median PFS about 13 months were observed in anti–PD-1–naive advanced melanoma; activity was lower after prior anti–PD-1 for advanced disease. Safety was broadly similar to PD-1 monotherapy but with a higher incidence of adrenal insufficiency; grade ≥3 TRAEs occurred in about 22%, with treatment discontinuation in approximately 13%. Control arm: relatlimab plus nivolumab, an approved fixed-dose combination of LAG-3 and PD-1 blockade for unresectable or metastatic melanoma.
Outcomes: Primary endpoint is objective response rate per RECIST 1.1 by blinded independent central review. Key secondary endpoints include PFS by BICR, overall survival, time to death from any cause, duration of response, disease control rate, and corresponding investigator-assessed endpoints. Safety endpoints include incidence of TEAEs, SAEs, immune-mediated AEs, lab abnormalities, treatment interruptions/discontinuations, and TEAEs leading to death. Pharmacokinetic endpoints measure serum concentrations of fianlimab and cemiplimab. Immunogenicity endpoints evaluate incidence and titers of anti-drug and neutralizing antibodies to both agents. Follow-up for efficacy and safety extends up to 72 months.
Burden on patient: Moderate. As a phase 3 immunotherapy trial with two IV combination regimens, patients can expect regular infusion visits, serial radiographic assessments per RECIST, and comprehensive safety monitoring including labs and cardiac markers as indicated. Additional burden arises from pharmacokinetic sampling and repeated immunogenicity blood draws over time. No mandated invasive procedures beyond standard-of-care imaging and labs are described, and there are no investigational oral agents, but the long follow-up period (up to 6 years) and immunotherapy-specific safety surveillance contribute to ongoing visit frequency and monitoring needs.
Last updated: Oct 2025
Key Inclusion Criteria:
1. Participants with histologically confirmed unresectable stage III and stage IV (metastatic) melanoma per American Joint Committee on Cancer (AJCC), eighth revised edition.
2. Participants must not have received prior systemic therapy for unresectable or metastatic melanoma as described in the protocol.
3. Measurable disease per RECIST version 1.1.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
5. Adequate bone marrow, hepatic, and kidney function
6. Known B-Rapidly Accelerated Fibrosarcoma protein (BRAF) V600 mutation status or submitted sample for BRAF V600 mutation assessment as described in the protocol
Key Exclusion Criteria:
Medical Conditions:
1. Uveal, acral or mucosal melanoma.
2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents as described in the protocol.
3. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection. Mild cancer-related immunodeficiency (such as immunodeficiency treated with gamma globulin and without chronic or recurrent infection) is allowed.
Prior/Concomitant Therapy:
4. Prior immune checkpoint inhibitor therapy other than anti-PD1/PD-L1 as described in the protocol
5. Systemic immune suppression as described in the protocol.
Other Comorbidities:
6. Participants with a history of myocarditis.
7. Troponin T (TnT) or troponin I (TnI) \>2x institutional upper limit of normal (ULN).
8. Active or untreated brain metastases or spinal cord compression as described in the protocol.
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply.
Québec, G1J 0J9, Canada
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London, Ontario, N6A 5W9, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Gilbert, Arizona, 85234, United States
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Chandler, Arizona, 85224, United States
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Little Rock, Arkansas, 72205, United States
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Los Alamitos, California, 90720, United States
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Rancho Mirage, California, 92270, United States
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Fullerton, California, 92835, United States
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Santa Barbara, California, 93105, United States
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Santa Monica, California, 90404, United States
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Orange, California, 92868, United States
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Sacramento, California, 95816, United States
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Los Angeles, California, 90024, United States
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San Francisco, California, 94143, United States
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Aurora, Colorado, 80045, United States
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Englewood, Colorado, 80113, United States
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Fort Collins, Colorado, 80528, United States
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Aurora, Colorado, 80045, United States
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New Haven, Connecticut, 06510, United States
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Tamarac, Florida, 33321, United States
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Jacksonville, Florida, 32256, United States
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Clermont, Florida, 34711, United States
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Tampa, Florida, 33612, United States
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Jacksonville, Florida, 32224, United States
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Columbus, Georgia, 31904, United States
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Athens, Georgia, 30607, United States
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Coeur d'Alene, Idaho, 83815, United States
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Park Ridge, Illinois, 60068, United States
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Hinsdale, Illinois, 60521, United States
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Peoria, Illinois, 61615, United States
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Fort Wayne, Indiana, 46825, United States
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Westwood, Kansas, 66205, United States
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Lexington, Kentucky, 40536, United States
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Baton Rouge, Louisiana, 70809, United States
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Columbia, Maryland, 21044, United States
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Detroit, Michigan, 48201, United States
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Ann Arbor, Michigan, 48109, United States
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Minneapolis, Minnesota, 55407, United States
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Fridley, Minnesota, 55432, United States
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St Louis, Missouri, 63128, United States
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St Louis, Missouri, 63106, United States
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St Louis, Missouri, 63110, United States
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Billings, Montana, 59102, United States
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Omaha, Nebraska, 68130, United States
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Las Vegas, Nevada, 89148, United States
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Hackensack, New Jersey, 07601, United States
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New Brunswick, New Jersey, 08901, United States
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Paramus, New Jersey, 07652, United States
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Albany, New York, 12206, United States
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Durham, North Carolina, 27710, United States
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Charlotte, North Carolina, 28204, United States
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Asheville, North Carolina, 28806, United States
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Charlotte, North Carolina, 28204, United States
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Charlotte, North Carolina, 28204, United States
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Wilmington, North Carolina, 28401, United States
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Cincinnati, Ohio, 45242, United States
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Cleveland, Ohio, 44106, United States
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Tulsa, Oklahoma, 74146, United States
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Portland, Oregon, 97227, United States
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Eugene, Oregon, 97401, United States
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Portland, Oregon, 97239, United States
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Philadelphia, Pennsylvania, 19111, United States
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Easton, Pennsylvania, 18045, United States
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Pittsburgh, Pennsylvania, 15232, United States
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Providence, Rhode Island, 02903, United States
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Greenville, South Carolina, 29607, United States
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Nashville, Tennessee, 37203, United States
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Nashville, Tennessee, 37203, United States
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Chattanooga, Tennessee, 37404, United States
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Knoxville, Tennessee, 37920, United States
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Fort Worth, Texas, 76104, United States
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Lubbock, Texas, 79410, United States
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Dallas, Texas, 75246, United States
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Austin, Texas, 78731, United States
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Austin, Texas, 78705, United States
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Bedford, Texas, 76022, United States
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Fort Worth, Texas, 76104, United States
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Grapevine, Texas, 76051, United States
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Harlingen, Texas, 78550, United States
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Longview, Texas, 75601, United States
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McAllen, Texas, 78503, United States
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Dallas, Texas, 75230, United States
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Weslaco, Texas, 78596, United States
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Palestine, Texas, 75801, United States
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Tyler, Texas, 75702, United States
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Tyler, Texas, 75701, United States
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Houston, Texas, 77030, United States
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Salt Lake City, Utah, 84112, United States
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Roanoke, Virginia, 24014, United States
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Charlottesville, Virginia, 22908, United States
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Fairfax, Virginia, 22031, United States
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Richmond, Virginia, 23298, United States
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Norfolk, Virginia, 23502, United States
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Seattle, Washington, 98104, United States
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Edmonds, Washington, 98026, United States
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Issaquah, Washington, 98029, United States
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Morgantown, West Virginia, 26506, United States
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Madison, Wisconsin, 53792, United States
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Tucson, Arizona, 85711, United States
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