Fianlimab Combo Does Not Significantly Improve PFS in Advanced Melanoma

Results from a phase 3 trial (NCT05352672) evaluating the combination of fianlimab, an investigational LAG-3 inhibitor, with cemiplimab-rwlc (Libtayo) as a first-line treatment for patients with unresectable locally advanced or metastatic melanoma did not meet statistical significance for the primary end point of improvement in progression-free survival (PFS).¹

Efficacy Results

The trial evaluated 2 dose levels of fianlimab (400 mg and 1600 mg) in combination with cemiplimab at 350 mg, administered every 3 weeks. Additionally, placebo plus 200 mg of pembrolizumab (Keytruda) or placebo plus 350 mg of cemiplimab was given every 3 weeks. The primary end point analysis revealed that neither dose level of the combination demonstrated a statistically significant improvement in PFS compared to the control arm.

The median PFS in the high-dose combination (1600 mg; n = 508) was 11.5 months (95% CI, 6.3-16.8) with an HR relative to pembrolizumab of 0.845 (95% CI, 0.709-1.008; P = .0627). The low-dose combination (400 mg; n = 422) had a median PFS of 9.6 months (95% CI, 6.2-13.9) with an HR relative to pembrolizumab of 0.931 (95% CI, 0.773-1.112; P = .4661). The median PFS for the pembrolizumab monotherapy (n = 462) was 6.4 months (95% CI, 4.4-11.1), and in the cemiplimab monotherapy arm (n = 154), it was 6.3 months (95% CI, 4.0-17.2).

A phase 3 head-to-head trial of fianlimab vs nivolumab plus relatlimab-rmbw (Opdualag) is currently ongoing.

Safety Profile

While the trial did not meet its primary efficacy end point, the press release stated that the safety profile of the fianlimab/cemiplimab combination appeared consistent with what has been observed in previous studies of these agents. The company noted that no new or unexpected safety signals emerged during the trial.

Trial Design and Objectives

The phase 3 study was designed to evaluate whether adding fianlimab to cemiplimab could improve outcomes compared with pembrolizumab in patients with melanoma.²

The trial enrolled 1546 patients with unresectable locally advanced or metastatic melanoma who had not received prior systemic therapy for their advanced disease. Patients were randomly assigned to receive either the fianlimab/cemiplimab combination at 2 different dose levels or treatment in a control arm. The primary end point was PFS, and secondary end points included overall survival, objective response rate, and disease control rate.

Patients were eligible for treatment if they had histologically confirmed unresectable stage III and stage IV metastatic melanoma, no prior systemic therapy for advanced unresectable disease, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 to 1 if they were adults or a Karnofsky performance status of 70 or more if they were 16 years or older, and an anticipated life expectancy of at least 3 months.

Patients were excluded from enrollment if they had uveal melanoma; ongoing or recent autoimmune disease that required systemic treatment with immunosuppressive agents; uncontrolled infection with HIV, hepatitis B, or hepatitis C; unknown BRAF V600 mutation status; or systemic immune suppression. Having myocarditis was also grounds for exclusion from the trial.

References

1. Regeneron provides update on phase 3 trial of fianlimab (LAG-3 Inhibitor) combination in first-line unresectable or metastatic melanoma. News release. May 15, 2026. Accessed May 19, 2026. https://tinyurl.com/35ef8n35
2. Clinical study of fianlimab in combination with cemiplimab versus pembrolizumab in adolescent and adult patients with previously untreated unresectable locally advanced or metastatic melanoma. ClinicalTrials.gov. Updated April 22, 2026. Accessed May 19, 2026. https://tinyurl.com/4b5mexr7