Merck's LAG-3 and Keytruda combo fails Phase 3 in colorectal cancer

Merck’s efforts to combine its PD-1 blockbuster Keytruda with an experimental LAG-3 inhibitor faced a significant setback on Wednesday morning. A Phase 3 study testing the LAG-3 program favezelimab in combination with Keytruda failed to meet its primary endpoint. The study did not show an improvement in overall survival rates compared to the standard of care. This trial focused on patients with metastatic colorectal cancer who had previously received PD-L1 therapy and whose cancer cells were considered “microsatellite stable.”

This development represents a notable challenge for Merck, which has been striving to keep up with Bristol Myers Squibb in the race to develop an approved dual PD-1/LAG-3 combination therapy. However, the specific clinical setting of microsatellite stable metastatic colorectal cancer has proven to be quite challenging. Last year, Bristol Myers Squibb's similar treatment, Opdualag, which combines Opdivo with relatlimab, also did not succeed in a Phase 3 study targeting the same type of cancer.

Beyond colorectal cancer, Merck has broader ambitions for the combination therapy of Keytruda and favezelimab. The company is actively exploring its potential in treating bladder cancer, melanoma, hematological malignancies, and esophageal cancer, among other types of cancer.

This recent trial failure underscores the complexity and difficulty of developing effective combination therapies for certain types of cancer, especially those like microsatellite stable metastatic colorectal cancer. Despite the setback, Merck remains committed to its broader oncology strategy and the pursuit of innovative treatments to improve patient outcomes across various cancer types.