Multicenter phase 1b-2 trial of first-line durvalumab and tremelimumab with chemotherapy for RAS-mutated metastatic colorectal cancer

Although patients with microsatellite instable metastatic colorectal cancer (mCRC) benefti from immune checkpoint blockade, chemotherapy with targeted therapy remains the only therapeutic option for microsatellite stable (MSS) tumors. The single-arm multicenter phase 1b-2 MEDITREME trial in France evaluated the combination of durvalumab and tremelimumab with mFOLFOX6 chemotherapy as first-line treatment for RAS-mutated metastatic colorectal cancer. Safety was the primary objective of phase 1b; no safety issue was observed. The phase 2 primary objective of efficacy in terms of 3-month progression-free survival in patients with MSS tumors was met, with 3-month PFS rate of 90.7% (95% CI 79.2-96.0). The response rate was 64.5%; the median PFS was 8.2 months, and median overall survival was not met in patients with MSS tumors. There were higher tumor mutational burden and lower genomic instability in responders. The authors conclude that the combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC.