Bristol Myers Squibb's Opdualag comes up short in late-stage colorectal cancer trial

Bristol Myers Squibb’s PD-1/LAG3 combo Opdualag has more than proved its worth in melanoma since its first-in-class approval in 2022. Now, the drug's first venture outside the melanoma arena has come up short, as the company scrapped a phase 3 trial in metastatic colorectal cancer (mCRC). 

After a planned analysis by an independent data monitoring committee, the trial, coded Relativity-123, was deemed unlikely to meet its primary endpoints in the treatment of microsatellite-stable (MSS) mCRC patients whose disease has progressed following at least one prior line of therapy, BMS said in a press release.

Bristol's move to end the study was not attributed to any safety concerns, the company said. Studies of the combo in other tumor types will continue “as planned.”

“While we know immunotherapies have historically demonstrated limited efficacy in MSS colorectal cancers, we had hoped to demonstrate meaningful clinical benefit in this patient population and are disappointed in this outcome,” vice president and global program lead Jeffrey Walch, M.D., Ph.D., noted in the release. “We continue to be committed to the development of I-O therapies, including Opdivo (nivolumab) and Yervoy (ipilimumab).”

In a Monday note to clients, William Blair analyst Matt Phipps, Ph.D., said he had always had low expectations for LAG3-containing therapies in mCRC given their weak data in early-phase trials. Instead, the analyst called upcoming phase 2 results in first-line non-small cell lung cancer (NSCLC) the “more important” near-term readout.

“The Opdualag launch in metastatic melanoma has been strong, and with exclusivity well into the 2030s, Opdualag offers a meaningful opportunity to extend the PD-1 franchise for Bristol Myers,” Phipps wrote.

Opdualag, which is a combo of BMS’ PD-1 inhibitor Opdivo and LAG3 antibody relatlimab, scored its initial approval last March in unresectable or metastatic melanoma. Since then, the company has shown the drug’s benefits in several melanoma patient groups, proving consistency in trial endpoints across patient subgroups, Mark Rutstein, M.D., vice president of Opdivo development at BMS, said in an interview at the time.

The company has projected over $4 billion in 2029 sales from Opdualag.