ESMO 2024 – Regeneron's fianlimab do-over

Regeneron's hopes to beat Bristol Myers Squibb in Lag3 have taken a twist, with the company blaming a "clerical error" for declining results in melanoma patients receiving its contender fianlimab, plus Libtayo, following perioperative PD-(L)1 therapy.

It was these patients who last year helped fianlimab's case, but this year’s ESMO meeting showed much less impressive results. Regeneron is well behind, with pivotal data in first-line melanoma due next year and results with a fixed-dose combination not expected until 2027. The group will need something special to overtake Bristol, which has had its Lag3/PD-1 combo, Opdualag, approved in melanoma since 2022.

Perioperative waning

Regeneron's data came from a phase 1 trial of fianlimab, with or without Libtayo, in solid tumours. Zooming in on melanoma, the study had already impressed in PD-(L)1-naive patients, and results presented at ASCO 2023 also suggested a benefit in those who had previously received perioperative checkpoint inhibitors but subsequently relapsed; here the ORR was 62%, with eight of 13 patients responding.

The latest update, presented in an ESMO poster this year, concerned long-term follow-up from the same study. While response rates in the other melanoma cohorts held up, in the post-PD-(L)1 group the ORR shrank to 39% (7/18 responses).

During an interview at ESMO Regeneron put this development down to a “technicality”. Essentially, some patients classed as responders by investigator assessment couldn’t be included in the independent analysis, because their disease was deemed unmeasurable at baseline.

“Recist doesn’t do a good job of assessing lymph node disease,” Israel Lowy, Regeneron’s head of translational sciences, oncology, told ApexOnco. “So there were some discrepancies between the baseline assessments done by the blinded [analysis] versus the investigator, which meant there were several patients who couldn’t be accounted for.”

He noted that progression-free survival was a more important endpoint than ORR, and pointed to a PFS analysis showing the PD-(L)1 pretreated patients, along with the overall study population, doing “extremely well”.

Across all cohorts the ORR was 57% and estimated median PFS was 24 months.

With the usual caveats about cross-trial comparisons, fianlimab plus Libtayo could still have an edge over Opdualag, which showed an ORR of 43% and a median PFS of 10.1 months in its pivotal Relativity-047 study.

However, Regeneron needs to get to market first, and this looks some way off. The pivotal trial of fianlimab plus Libtayo in first-line melanoma isn't due to read out until the second half of next year, Lowy said; data had once been expected in 2024.

And the company also hopes to launch a fixed-dose combination, a phase 3 study of which isn’t set to complete until 2027.

Notable studies of fianlimab in melanoma

Notes: EFS=event-free survival; ORR=overall response rate; pCR=pathologic complete response; PFS=progression-free survival; RFS=relapse-free survival. Source: OncologyPipeline & company communications.