Fianlimab flunks its big test

Delays and changes to clinical trials are rarely a good sign, and Regeneron showed this again with the failure of its anti-Lag3 MAb fianlimab in its lead use, first-line melanoma, announced after market close on Friday.In the phase 3 R3767-ONC-2011 study, a combination with Libtayo failed to outdo Keytruda monotherapy on the primary endpoint of progression-free survival. Regeneron is still clinging to the hope of victory in a head-to-head trial against Bristol Myers Squibb’s anti-Lag3/PD-1 combo Opdualag – but even usually bullish sellside analysts are assuming the worst for fianlimab.The news comes hot on the heels of failures in first-line lung cancer. Regeneron, which is looking to replace its key eye disease drug Eylea, saw its stock open down 10% on Monday.Melanoma melancholyR3767-ONC-2011 tested two doses of fianlimab, 400mg and 1,600mg, both plus Libtayo at 350mg. Both doses failed to show an improvement on PFS versus Keytruda, although Regeneron pointed to a “numeric improvement” with high-dose fianlimab.Median PFS was 11.5 months and 9.6 months in the high and low-dose fianlimab arms respectively, versus 6.4 months with Keytruda, giving respective hazard ratios of 0.85 and 0.93.The trial also included a Libtayo monotherapy arm, which produced mPFS of 6.3 months, in line with the Keytruda result.The signs for this study had looked inauspicious for some time. Results had once been expected in 2024, but these were pushed back to the second half 2025, then to late 2025/early 2026. More recently, Regeneron tinkered with the trial’s protocol, adding patients to the PFS analysis to increase powering, owing to a slow rate of events in the initial cohort of subjects enrolled.Evercore ISI’s Cory Kasimov had previously estimated around $900m in risk-adjusted peak sales for fianlimab in melanoma, but has now removed the project from his model, despite the ongoing head-to-head study against Opdualag.Opdualag testThat’s testing high-dose fianlimab (presumably 1,600mg) plus Libtayo; the primary endpoint is overall response rate, with PFS and OS as key secondaries. A hit here could salvage fianlimab, but results could be some way off: the trial is still enrolling, with primary completion set for March 2027.Bristol’s drug, a fixed dose combo of relatlimab and nivolumab, is US approved for first-line melanoma based on the Relativity-047 trial. That reported an ORR of 43% and a mPFS of 10.1 months, beating Opdivo monotherapy. However, the study missed on OS.Beyond Opdualag, Lag3 has seen various setbacks, with Merck & Co notably discontinuing its contender favezelimab in 2024. The Keyform-008 in classical Hodgkin lymphoma patients progressed on prior PD-1 inhibitors will feature at the upcoming EHA meeting.As for fianlimab, in addition to the Opdualag head-to-head study, a phase 3 in adjuvant melanoma versus Keytruda is also ongoing, with data set for the second half of this year. But hopes cannot now be high for this project. Phase 3 trials of fianlimab in melanomaTrialSettingRegimenNoteR3767-ONC-20111st-line melanoma400mg or 1,600mg + Libtayo, vs Keytruda (also included Libtayo monoRx arm)Failed May 2026; data had once been expected in 2024R3767-ONC-2055Adjuvant melanoma“Low dose” or “high dose” + Libtayo, vs KeytrudaFirst interim analysis passed in Q1 2026; data due H2 2026R3767-ONC-221221st-line melanoma"High dose” + Libtayo (fixed-dose combo), vs OpdualagEnrolling; completes Mar 2027Source: OncologyPipeline & company release.