Regeneron’s Phase 3 fianlimab combination misses primary endpoint in first-line advanced melanoma

Regeneron Pharmaceuticals has reported that its Phase 3 trial of the LAG-3 inhibitor fianlimab, given in combination with the PD-1 inhibitor cemiplimab, failed to reach statistical significance on its primary endpoint of progression-free survival (PFS) versus pembrolizumab monotherapy in previously untreated patients with unresectable locally advanced or metastatic melanoma. No new safety signals emerged with the fianlimab-based regimen.

The study tested two dose levels of the fianlimab plus cemiplimab combination against pembrolizumab as the comparator, with a separate cemiplimab monotherapy arm included to characterize the contribution of each component rather than for formal statistical comparison.

The high-dose fianlimab combination delivered a median PFS of 11.5 months (95% CI 6.3–16.8) compared with 6.4 months (95% CI 4.4–11.1) on pembrolizumab — a numerical improvement of 5.1 months that nonetheless missed the prespecified statistical threshold, with a hazard ratio of 0.845 (95% CI 0.709–1.008; p=0.0627). The low-dose combination produced a median PFS of 9.6 months (95% CI 6.2–13.9) against a concurrently randomized pembrolizumab subset (n=421), yielding a hazard ratio of 0.931 (95% CI 0.773–1.122; p=0.4661). In the descriptive cemiplimab monotherapy arm (n=154), median PFS was 6.3 months (95% CI 4.0–17.2).

Full results are due to be presented at an upcoming medical meeting.

Regeneron also confirmed that a separate Phase 3 head-to-head study, evaluating the high-dose fianlimab plus cemiplimab regimen against Opdualag® (nivolumab and relatlimab-rmbw) in the same first-line unresectable or metastatic melanoma setting, remains ongoing.

The combination of fianlimab and cemiplimab is investigational, and its safety and efficacy have not been evaluated by any regulatory authority.

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Related Topics and Keywords

first-line advanced melanoma, melanoma, Phase 3 fianlimab, Phase 3 trial, Regeneron, Regeneron Pharmaceuticals