Investigational Drug
fianlimab
TrialFetch AI Analysis
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Overview
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)
Mechanism of action
- Target: Lymphocyte activation gene-3 (LAG‑3), an immune checkpoint receptor expressed on activated T cells. Fianlimab binds LAG‑3 to relieve inhibitory signaling; when combined with PD‑1 blockade (cemiplimab), dual checkpoint inhibition aims to enhance antitumor T‑cell activity. (ascopubs.org)
Efficacy
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)
Safety
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)
Further reading
- Phase I study in advanced melanoma (peer‑reviewed, full text): Journal of Clinical Oncology. (ascopubs.org)
- ASCO 2021 meeting abstract reporting early melanoma activity and safety. (ascopubs.org)
- First‑in‑human dose‑escalation study (mechanism, dose selection): Clinical Cancer Research. (aacrjournals.org)
- Phase 3 trial synopsis: first‑line unresectable/metastatic melanoma (NCT05352672). (ascopubs.org)
- Phase 3 trial synopsis: adjuvant high‑risk resected melanoma (NCT05608291). (ascopubs.org)
- Phase 2/3 NSCLC trial synopses (NCT05785767; NCT05800015). (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
Active trials using fianlimab
Found 8 active trials using this drug:
TrialFetch AI summary: Randomized first-line study for adults with PD-L1 CPS ≥1 recurrent/metastatic HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx, with measurable disease and ECOG 0–1, no prior systemic therapy for R/M disease, and stratified by HPV status. Patients receive fianlimab, an anti–LAG-3 immune checkpoint antibody, plus cemiplimab anti–PD-1 versus cemiplimab plus placebo.
ClinicalTrials.gov ID: NCT06769698
TrialFetch AI summary: Adults with oligometastatic clear cell renal cell carcinoma with 1–5 RECIST-measurable lesions amenable to definitive SBRT, including the primary tumor if present, receive SBRT to all disease sites and are then randomized to cemiplimab, an anti–PD-1 antibody, with or without fianlimab, an anti–LAG-3 antibody. Treatment is given every 3 weeks for up to 1 year to test whether dual checkpoint blockade improves 1-year progression-free survival after SBRT.
ClinicalTrials.gov ID: NCT07223541
TrialFetch AI summary: Adults with previously untreated advanced/unresectable or metastatic clear cell RCC (all IMDC risk groups; KPS ≥70; measurable disease) are randomized to fianlimab (anti–LAG-3) plus cemiplimab (PD-1 inhibitor) with or without ipilimumab (CTLA-4 inhibitor) versus standard ipilimumab plus nivolumab (PD-1 inhibitor, with nivolumab maintenance). The trial evaluates ORR and safety of LAG-3/PD-1 dual blockade (± CTLA-4) as first-line immunotherapy in this population.
ClinicalTrials.gov ID: NCT07188896
TrialFetch AI summary: Adults with platinum‑resistant high‑grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer (ECOG 0–1) are randomized to ubamatamab (MUC16×CD3 T‑cell–redirecting bispecific) with prophylactic sarilumab, given alone or combined with bevacizumab, cemiplimab plus fianlimab (PD‑1/LAG‑3 blockade), or pegylated liposomal doxorubicin. Excludes clear cell/mucinous/carcinosarcoma histologies and active CNS disease; primary endpoint is RECIST ORR.
ClinicalTrials.gov ID: NCT06787612
TrialFetch AI summary: Adults with unresectable stage III/IV or metastatic cutaneous or mucosal melanoma that has progressed on prior PD-1/PD-L1 therapy (including after PD-1+LAG-3) receive triplet immune checkpoint blockade: fianlimab (anti–LAG-3), cemiplimab (anti–PD-1), and ipilimumab (anti–CTLA-4). Excludes uveal melanoma and untreated/leptomeningeal CNS disease; definitively treated brain metastases allowed.
ClinicalTrials.gov ID: NCT06594991
TrialFetch AI summary: Adults with untreated unresectable stage III or metastatic cutaneous melanoma (ECOG 0–1, measurable disease; excludes uveal/acral/mucosal melanoma, active brain mets, and significant autoimmune disease) are randomized to fixed-dose fianlimab (anti–LAG-3) plus cemiplimab (anti–PD-1) versus the approved relatlimab (anti–LAG-3) plus nivolumab (anti–PD-1) first-line. Primary endpoint is BICR-assessed ORR, with key secondary PFS/OS and safety.
ClinicalTrials.gov ID: NCT06246916
TrialFetch AI summary: Adults with locally advanced cutaneous basal cell carcinoma of the head and neck where standard surgery would be unresectable or highly morbid receive neoadjuvant cemiplimab, an anti–PD-1 antibody, before planned surgery. A second cohort receives cemiplimab plus fianlimab, an anti–LAG-3 antibody, to assess whether dual checkpoint blockade improves tumor response and enables organ-preserving surgery.
ClinicalTrials.gov ID: NCT05929664
TrialFetch AI summary: Adults with MUC16-positive advanced ovarian, primary peritoneal/fallopian tube, or endometrial cancer after prior platinum (and prior anti–PD‑1 for endometrial) receive the investigational MUC16×CD28 costimulatory bispecific REGN5668 alone or combined with anti–PD‑1 cemiplimab, cemiplimab+anti–LAG‑3 fianlimab, or the MUC16×CD3 T‑cell engager ubamatamab (some cohorts with IL‑6R blocker sarilumab for CRS mitigation). Aims to enhance T‑cell activation against MUC16 tumors via CD28 costimulation with or without PD‑1/LAG‑3 blockade or CD3 engagement; key exclusions include prior MUC16‑targeted therapy, active autoimmune/CNS disease, and significant cardiac disease.
ClinicalTrials.gov ID: NCT04590326
