Upon Opdualag’s approval in 2022 as a first-in-class cancer immunotherapy, Bristol Myers Squibb was anxious to explore its potential in a variety of indications. But so far, the company is striking out in its attempts to broaden its label.
On Thursday, BMS revealed that a phase 3 trial of Opdualag as an adjuvant treatment for patients with completely resected stage III and stage IV melanoma did not achieve its primary endpoint.
Opdualag—which is a combination of BMS’ PD-1 inhibitor Opdivo and its lymphocyte activation gene 3 (LAG-3) blocking antibody relatlimab—did not significantly improve recurrence-free survival (RFS) compared to Opdivo monotherapy.
The failure puts a dent in BMS’ plan to expand Opdualag’s ability to treat melanoma patients. Its current approval covers those age 12 and older with unresectable or metastatic melanoma.
This is the second major clinical defeat for Opdualag. Fourteen months ago, the company scrapped a phase 3 trial of Opdualag in metastatic colorectal cancer (mCRC).
“We are disappointed in the outcome of the RELATIVITY-098 trial and that LAG-3 inhibition in the adjuvant setting did not lead to the same improved efficacy outcomes seen in advanced melanoma,” Jeffrey Walch, M.D., Ph.D., BMS’ global program lead for Opdualag, said in a release. “Patients whose tumors are completely resected before treatment may not have sufficient antitumor T cells in place for Opdualag to have its maximal effect.”
Walsh added that BMS has high hopes for Opdualag in non-small cell lung cancer (NSCLC).
In the RELATIVITY 1093 trial, BMS will test Opdualag plus chemotherapy in patients with stage 4 or recurrent non-squamous NSCLC with PD-L1 expression between 1% and 49%. The trial will use a higher dose of relatlimab than in Opdualag’s FDA-approved melanoma indication and will use Merck’s Keytruda and chemo as the comparator.
Additionally, BMS plans to initiate another phase 3 trial this year for Opdualag in first-line, non-squamous NSCLC patients with PD-L1 expressions of at least 50%.
In 2024, Opdualag achieved sales of $928 million, which was a 48% increase from the previous year.
Regeneron is set to challenge BMS with its own LAG-3 inhibitor, fianlimab, which has shown enough promise for the company to launch four phase 3 programs, combining it with its PD-1 inhibitor Libtayo.