Another fianlimab fiasco for Regeneron

After several delays in recent years for Regeneron’s anti-Lag3 MAb fianlimab, the group has now admitted defeat in lung cancer. During its first-quarter results Regeneron disclosed that phase 2 data in first-line NSCLC didn’t justify pressing on into phase 3.

The big event for fianlimab remains pivotal results in first-line melanoma, which are still expected in the second quarter. However, more doubts are creeping in here, after it emerged that the company had changed the protocol of its trial owing to a slow rate of event accruals.

Although this might be a sign that fianlimab is improving progression-free survival, the primary endpoint, it’s also possible that patients in the control group are doing well. Overall, such developments are rarely a good sign.

Lung lack

In first-line NSCLC Regeneron had been carrying out two phase 2/3 trials: one testing fianlimab plus Libtayo versus Libtayo, and the other evaluating fianlimab plus Libtayo plus chemo, versus Libtayo plus chemo.

Data had once been expected by the end of 2024, and Regeneron had hoped to outdo Bristol Myers Squibb’s relatlimab/Opdivo combo, which flunked the phase 2 Relativity-104 trial.

But Regeneron first pushed back data to the first half of 2025, then to 2026 – and now the studies have been revealed as a bust.

Bristol, meanwhile, has marched into its own phase 3 trial, Relativity-1093, testing relatlimab plus Opdivo, versus Keytruda plus chemo, in PD-L1 expressers. The study, which doesn’t complete until 2030, was initially recruiting patients with of 1-49% expression, but this was changed to ≥1%.

Melanoma meddling

Melanoma remains the main hope to fianlimab, but there might now be reasons to be cautious here. The phase 3 R3767-ONC-2011 study tests fianlimab plus Libtayo, versus Keytruda in first-line disease, with a primary endpoint of progression-free survival, and overall survival a key secondary.

Data are expected in the second quarter, as before, but Evercore ISI’s Cory Kasimov noted that Regeneron has had to alter the trial’s protocol to keep this timing intact. Owing to a slow rate of events in the initial cohort of patients enrolled, known as the “PFS analysis set”, the company will use the full analysis set, which also includes around 360 patients from a so-called OS cohort. This OS cohort was added to increase the study’s powering.

This trial has also been delayed – results were once due in 2024, then moved back several times, before eventually being set for the first half of this year. At the very least, this shows that Regeneron’s initial powering assumptions were way off the mark. The company will have to hope that it’s nothing worse than this.

Bristol’s relatlimab/Opdivo combo is already FDA approved in first-line melanoma, where it’s branded Opdualag. However, the supporting Relativity-047 trial only hit on PFS, and narrowly missed on OS.

Opdualag has set the bar to beat here. Relativity-047 compared the Bristol combo against Opdivo, and found a hazard ratio of 0.75 on PFS, and 0.80 on OS. Opdualag sold $1.2bn in 2025.

Regeneron is also carrying out a phase 3 trial of fianlimab plus Libtayo versus Opdualag, but this is some way off completion. And an interim analysis of an adjuvant melanoma trial has also passed, with final analysis due later this year.

Phase 3 trials of fianlimab

Note: *phase 2/3. Source: OncologyPipeline.