Multinational phase 2 trial of nivolumab plus relatlimab for previously treated MSI-H/dMMR metastatic colorectal cancer

The multinational phase 2 CheckMate 142 trial evaluated the combination of nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) for previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer (MSI-H/dMMR mCRC). The investigator-assessed objective response rate was 50% (95% CI 36-65) and the disease control rate was 70% (55-82), with median time to response per investigator 2.8 months (range 1.3-33.1), and median duration of response 42.7 months (2.8-47.0+). The median progression-free survival per investigator was 27.5 months (95% CI 5.3-43.7) with a PFS rate at 3 years of 38%), and the median overall survival was not reached with median follow-up of 47.4 months, with a 56% OS rate at 3 years. Grade 3 or 4 treatment-related adverse events were reported in 14% of patients, and TRAEs leading to discontinuation in 8%. There were no grade 5 TRAEs. The authors conclude that the combination of nivolumab plus relatlimab provided durable clinical benefit and was well tolerated in previously treated patients with MSI-H/dMMR mCRC.