Trial: A Study to See if Giving Fianlimab and …

Trial Details

Sponsor: Regeneron Pharmaceuticals (industry)

Phase: 2

Start date: April 14, 2026

Planned enrollment: 120

Trial ID: NCT06769698

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: fianlimab (REGN3767)

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)

TrialFetch AI Analysis

Goal: The goal of this phase II study is to determine whether adding the LAG-3 inhibitor fianlimab to the PD-1 inhibitor cemiplimab improves antitumor activity compared with cemiplimab alone as first-line treatment for PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma that is not curable with local therapy. The primary endpoint is overall response rate, with additional evaluation of safety, durability of benefit, pharmacokinetics, and immunogenicity.

Patients: The study is enrolling adults with histologically confirmed recurrent or metastatic squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx, including selected cases of cervical nodal squamous cell carcinoma with occult primary as defined by the protocol. Tumors must have PD-L1 combined positive score of at least 1, measurable disease by RECIST v1.1, ECOG performance status 0 or 1, and adequate organ and marrow function. Patients with oropharyngeal cancer must have documented HPV status. Key exclusions include prior systemic therapy for recurrent or metastatic HNSCC, progression within 6 months of curative-intent systemic therapy for locoregionally advanced disease, nasopharyngeal, paranasal sinus, or salivary gland primaries, active or recently treated autoimmune disease, significant pneumonitis or interstitial lung disease history, significant cardiovascular disease, and need for immunosuppressive corticosteroids above physiologic doses.

Design: This is an industry-sponsored, randomized phase II treatment study with two cohorts defined by HPV status. Approximately 60 patients with HPV-positive HNSCC and approximately 60 patients with HPV-negative HNSCC will be enrolled. Within each cohort, patients are randomized 1:1 to fianlimab plus cemiplimab versus cemiplimab plus placebo. Response and progression are assessed by investigator evaluation using RECIST v1.1, and safety follow-up continues through 90 days after the last study treatment, with total study follow-up of approximately 58 months.

Treatments: The experimental arm receives a fixed-dose combination of fianlimab plus cemiplimab. Fianlimab is a fully human IgG4 monoclonal antibody targeting LAG-3, an inhibitory immune checkpoint expressed on activated and exhausted T cells; blockade of LAG-3 is intended to restore antitumor T-cell activity and may complement PD-1 inhibition. The most mature clinical data for fianlimab plus cemiplimab are in advanced melanoma, where a phase I study in anti–PD-1–naive advanced melanoma reported an objective response rate of about 61% and median progression-free survival of 13.3 months, with a safety profile broadly similar to PD-1 monotherapy but with notable adrenal insufficiency. The control arm receives cemiplimab plus placebo; cemiplimab is an anti–PD-1 monoclonal antibody that enhances antitumor immunity and is an established immune checkpoint inhibitor across several tumor types.

Outcomes: The primary outcome is overall response rate. Secondary efficacy outcomes include disease control rate, duration of response, and progression-free survival by investigator assessment. Safety outcomes include incidence and severity of adverse events, treatment-emergent adverse events, immune-mediated adverse events, treatment-related adverse events, adverse events of special interest, serious adverse events, adverse events leading to discontinuation, adverse events leading to death, and laboratory abnormalities graded by NCI-CTCAE v5.0. Additional endpoints include serum concentrations of cemiplimab and fianlimab and incidence and titers of anti-drug antibodies to fianlimab.

Burden on patient: The expected patient burden is moderate. Treatment involves intravenous immunotherapy visits and randomized assignment to an additional immune checkpoint inhibitor or placebo, with monitoring for immune-related toxicities similar to other checkpoint inhibitor trials. The study requires serial imaging for RECIST assessment, routine safety laboratories, adverse-event monitoring, and additional blood draws for pharmacokinetics and anti-drug antibody testing. Eligibility requires prior documentation of PD-L1 CPS and, for oropharyngeal cancers, HPV status; a new biopsy is not clearly mandated if adequate prior tissue-based results are available. Overall, the burden is greater than standard-of-care single-agent PD-1 therapy because of trial visits, blinded placebo-controlled administration, and research blood sampling, but lower than many early-phase studies that require intensive inpatient monitoring or mandatory serial biopsies.

Last updated: May 2026

Eligibility

Show Criteria

Key Inclusion Criteria:

1. Have histologically confirmed (by local pathology) R/M HNSCC that is considered incurable by local therapies

2. Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx (patients with cervical neck node SCC with occult primary as described in the protocol

3. PD-L1 expression Combined Positive Score (CPS) ≥1 documented with a previously PD-L1 obtained Immunohistochemistry (IHC) result prior to screening, as described in protocol

4. Oropharynx cancer participants only: HPV status, based on a previously documented result prior to screening, must have been established in a surgical biopsy specimen or a core biopsy specimen as described in the protocol

5. At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as described in the protocol

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. Adequate organ and bone marrow function as described in the protocol

Key Exclusion Criteria:

Medical Conditions

1. Participants who have Progressive Disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC as described in the protocol

2. Participants who have a primary tumor site of nasopharynx, paranasal sinus or salivary gland (any histology)

3. Head and neck SCC with unknown primary site as described in the protocol

4. Participants with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date as described in the protocol

5. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management

6. History or current evidence of significant cardiovascular disease including, myocarditis, congestive heart failure (as defined by New York Heart Association Functional Classification III and IV), unstable angina, serious uncontrolled arrhythmia, and myocardial infarction 6 months prior to study enrollment.

Prior/Concomitant Therapy

7. Participants who have received prior systemic anticancer therapy in the R/M HNSCC setting as described in the protocol

8. Participants with a condition requiring corticosteroid therapy (\>10 mg prednisone/prednisolone/day or equivalent) within 14 days of the first dose of study drug as described in the protocol

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: fianlimab (REGN3767)

Overview

Mechanism of action

Efficacy

Safety

Further reading

TrialFetch AI Analysis

Eligibility

Show Criteria

Sites (10)

Peter MacCallum Cancer Centre (PMCC)

Orlando Health

Emory University School of Medicine

Norton Cancer Institute

St. Elizabeth Healthcare

Oncology Hematology West P.C. dba Nebraska Cancer Specialists

Ohio State University

Vanderbilt-Ingram Cancer Center

Joe Arrington Cancer Research & Treatment Center

Inova Schar Cancer Institute