Sponsor: Regeneron Pharmaceuticals (industry)
Phase: 3
Start date: Sept. 9, 2024
Planned enrollment: 560
Fianlimab (REGN3767) is an investigational, fully human, hinge-stabilized IgG4 monoclonal antibody targeting lymphocyte activation gene-3 (LAG-3). It is being developed primarily with the anti–PD-1 antibody cemiplimab. As of September 22, 2026, fianlimab remains unapproved, and its strongest clinical evidence is in advanced melanoma. (aacrjournals.org)
LAG-3 is an inhibitory immune-checkpoint receptor expressed on activated T cells. Fianlimab binds LAG-3 and blocks its interaction with MHC class II, thereby reducing inhibitory signaling and restoring T-cell activation. Preclinical models showed greater antitumor activity when LAG-3 blockade was combined with cemiplimab-mediated PD-1 blockade. Its Fc region was engineered to minimize antibody-dependent cytotoxicity against LAG-3-expressing immune cells. (aacrjournals.org)
In a published phase 1 study, 98 patients with advanced melanoma who had not received anti–PD-1 therapy for advanced disease had an investigator-assessed objective response rate (ORR) of 61.2% with fianlimab plus cemiplimab and a median progression-free survival (PFS) of 13.3 months after 12.6 months’ median follow-up. ORRs were 63% in anti–PD-1-naïve patients, 63% in systemic-treatment-naïve patients, and 56% in patients previously treated in the neoadjuvant or adjuvant setting. Among 15 patients previously treated with anti–PD-1 therapy for advanced disease, ORR was 13.3% and median PFS was 1.5 months. (pubmed.ncbi.nlm.nih.gov)
Longer follow-up of the 98-patient population, reported in a 2026 conference proceeding, found a blinded-independent-review ORR of 57%, including a 25% complete-response rate; median PFS was 24 months, while median overall survival had not been reached. These single-arm findings require interpretation alongside randomized evidence. (scholarlycommons.henryford.com)
In a 1,546-patient randomized phase 3 trial in previously untreated unresectable or metastatic melanoma, neither tested dose of fianlimab plus cemiplimab significantly improved PFS over pembrolizumab. Median PFS was 11.5 months with high-dose fianlimab, 9.6 months with low-dose fianlimab, and 6.4 months with pembrolizumab. For the high-dose comparison, the hazard ratio was 0.845 (95% CI 0.709–1.008; p=0.0627). These results were disclosed by the manufacturer in May 2026 and had not yet been presented as a peer-reviewed publication in the sources reviewed. (investor.regeneron.com)
In the published melanoma phase 1 study, grade 3 or higher treatment-emergent adverse events occurred in 44% of anti–PD-1-naïve patients, while grade 3 or higher treatment-related events occurred in 22%. Common events included fatigue, nausea, diarrhea, rash and pruritus. Adrenal insufficiency occurred in 12% overall and was grade 3–4 in 4%, a higher incidence than generally reported with PD-1 monotherapy. Treatment-related adverse events caused discontinuation in 13%; two treatment-related deaths were reported. (pmc.ncbi.nlm.nih.gov)
The phase 3 announcement stated that no new safety signals were identified, but detailed safety results were not provided. (investor.regeneron.com)
Last updated: Sep 2026
Goal: Compare the antitumor activity and safety of fianlimab plus cemiplimab with relatlimab plus nivolumab in unresectable or metastatic melanoma.
Patients: Participants with histologically confirmed unresectable stage III or stage IV melanoma, measurable disease, ECOG performance status 0–1, and no prior systemic therapy for unresectable or metastatic disease. BRAF V600 status must be known or assessed. Key exclusions include uveal, acral, or mucosal melanoma; active or untreated brain metastases; clinically significant autoimmune disease requiring systemic immunosuppression; and a history of myocarditis.
Design: Randomized, 1:1, active-comparator trial with follow-up for outcomes up to 72 months.
Treatments: Participants receive either the fixed-dose combination of fianlimab and cemiplimab or relatlimab plus nivolumab. Fianlimab is an investigational anti–LAG-3 antibody that blocks inhibitory LAG-3 signaling on T cells; cemiplimab blocks PD-1. In a single-arm phase 1 melanoma cohort without prior anti–PD-1 therapy for advanced disease, the combination produced a 61.2% investigator-assessed response rate, but a separate phase 3 comparison against pembrolizumab did not significantly improve progression-free survival. Relatlimab plus nivolumab is an approved LAG-3/PD-1 checkpoint-inhibitor combination for melanoma.
Outcomes: The primary endpoint is objective response rate by blinded independent central review using RECIST 1.1. Secondary measures include progression-free and overall survival, duration of response, disease control, investigator-assessed tumor outcomes, adverse events and laboratory abnormalities, serum drug concentrations, and anti-drug and neutralizing antibodies.
Burden on patient: Moderate. Treatment and serial tumor assessments are broadly consistent with care for advanced melanoma, but trial participation adds scheduled safety monitoring and blood draws for pharmacokinetics and immunogenicity. Visits and follow-up may continue for an extended period; the supplied information does not specify dosing or scan frequency or require research biopsies.
Last updated: Sep 2026
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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Montreal, Quebec, H3T 1E2, 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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Redlands, California, 92373, 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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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, 48202, 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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Status: Recruiting
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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Lebanon, New Hampshire, 03756, 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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Columbus, Ohio, 43210, 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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Houston, Texas, 77030, United States
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Salt Lake City, Utah, 84112, United States
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Fairfax, Virginia, 22031, 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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Kennewick, Washington, 99336, 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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Status: Recruiting
Tucson, Arizona, 85711, United States
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Status: Withdrawn
Columbus, Georgia, 31904, United States
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Status: Withdrawn
Tyler, Texas, 75701, United States
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Status: Withdrawn