Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) study (NRG- GI004/SWOG-S1610): A randomized phase III study of mFOLFOX6/bevacizumab combination chemotherapy with or without atezolizumab or atezolizumab monotherapy in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) metastatic colorectal cancer (mCRC).

TPS3615Background: DNA mismatch repair defect (dMMR) colorectal cancer (CRC) cells are highly immunogenic. Preclinical data showed that oxaliplatin-containing chemotherapy in combination with anti-VEGF enhances the antitumor activity of programmed cell death-1 (PD-1) pathway blockade in murine CRC models. Prior phase I study showed that mFOLFOX6/bevacizumab (bev) plus atezolizumab was well tolerated and enhanced intratumoral infiltration of CD8+ T cells. We hypothesize that the dMMR subset of CRC may be effectively targeted with the combination of PD-1 pathway blockade and mFOLFOX6/bev to promote tumor regression. Methods: This is a prospective randomized phase III open-label trial. Patients (pts) (N=347) with metastatic dMMR CRC will be randomized to 3 trial arms (1:1:1): mFOLFOX6/bev; atezolizumab monotherapy; or mFOLFOX6/bev plus atezolizumab. Stratification factors include BRAF status, metastatic site, and prior adjuvant therapy for CRC. Primary objective is to evaluate the efficacy of mFOLFOX6/bev/at...