Merck Discontinues TIGIT and LAG-3 Programs Amid Efficacy Concerns

Program Discontinuation:
Merck has announced the discontinuation of its clinical development programs for vibostolimab (an anti-TIGIT antibody) and favezelimab (an anti-LAG-3 antibody), which were being evaluated in combination with pembrolizumab (Keytruda) for various cancers35.

Efficacy Concerns:
The decision was made due to the failure of these combinations to meet primary endpoints in several Phase 3 trials, including KeyVibe-003 and KeyVibe-007 for non-small cell lung cancer (NSCLC) and KEYFORM-007 for colorectal cancer235.

Safety Profile:
While the safety profiles of vibostolimab and favezelimab were consistent with previous studies, more immune-related adverse events were observed with the fixed-dose combinations compared to Keytruda alone35.

Impact on Keytruda:
The discontinuation of these programs may slow Merck's push into new therapeutic spaces, such as microsatellite stable (MSS) colorectal cancer, where Keytruda has not yet secured a strong foothold2.

Industry Context:
Other companies, including Bristol Myers Squibb and Roche, have also faced challenges with TIGIT and LAG-3 programs, highlighting the difficulties in expanding checkpoint inhibitor therapies beyond established indications23.

Sources:

2. https://www.biospace.com/drug-development/mercks-keytruda-combo-fails-in-phase-iii-colorectal-cancer-study

3. https://www.oncologypipeline.com/apexonco/more-bad-vibes-kill-mercks-tigit-and-lag3

5. https://www.merck.com/news/merck-provides-update-on-keyvibe-and-keyform-clinical-development-programs-evaluating-investigational-vibostolimab-and-favezelimab-fixed-dose-combinations-with-pembrolizumab/