Another setback for Opdualag's post-melanoma plan

Bristol Myers Squibb’s Opdualag is the only Lag3/PD-1 combo approved, in melanoma, but expanding beyond this niche has proven tricky. Another failure came on Friday in microsatellite-stable metastatic colorectal cancer, where the Relativity-123 study was stopped for futility.

During its third-quarter results, Bristol also quietly slipped out a miss in second-line liver cancer; a study in first-line liver is ongoing. Opdualag could soon come under threat, with Regeneron’s Lag3 project fianlimab looking like it might have the edge in melanoma, according to data at this year’s ASCO meeting. However, fianlimab’s phase 3 melanoma studies are not due to yield data until 2025.

Outside melanoma, Regeneron’s main focus, for now, appears to be lung cancer, another indication Bristol has got to first; data are due next year from the latter’s first-line study of relatlimab plus Opdivo plus chemo.

One question Regeneron is facing is how to combine fianlimab and its PD-1 inhibitor Libtayo – the group has previously told ApexOnco that, like Bristol, it’s looking at a fixed-dose combination.

Merck & Co is trying something similar with its Lag3 inhibitor favezelimab, testing it in combo with its mega-blockbuster Keytruda. Merck has a chance to succeed where Bristol fell short: the project’s most advanced indication is colorectal cancer, where a phase 3 trial of a Keytruda/favezelimab coformulation is set to read out next year.

Favezelimab is also in phase 3 in Hodgkin’s lymphoma; Opdualag is at an earlier stage here, while fianlimab doesn't appear to be being tested. 

In addition, Merck is trialling favezelimab in NSCLC, SCLC, melanoma, and bladder, oesophageal and renal cancers, according to its third-quarter 2023 presentation.

Meanwhile, several Lag3 x PD-1 bispecifics are in development, including Roche’s tobemstomig and Macrogenics’ tebotelimab.

Beyond melanoma? Notable Opdualag, fianlimab and favezelimab trials

Source: OncologyPipeline & company presentations.