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).

<jats:p> TPS728 </jats:p><jats:p> Background: Deficient DNA mismatch repair (dMMR) colorectal cancer (CRC) cells are highly immunogenic. Preclinical data showed that oxaliplatin-containing chemotherapy combined with anti-VEGF enhances antitumor activity of programmed cell death-1 (PD-1) pathway blockade in murine CRC models. Prior phase I study showed mFOLFOX6/ bevacizumab (bev) + atezolizumab (atezo) was well tolerated and enhanced intratumoral infiltration of CD8<jats:sup>+</jats:sup> T cells. We hypothesize that the dMMR subset of CRC may be effectively targeted with combination of PD-1 pathway blockade and mFOLFOX6/bev to promote tumor regression. Methods: This is a prospective randomized phase III open-label trial. Pts (N=347) with mCRC dMMR will be randomized to 3 trial arms (1:1:1): mFOLFOX6/bev; atezo monotherapy; or mFOLFOX6/bev + atezo. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary objective is to evaluate efficacy of mFOLFOX6/bev/atezo and atezo monotherapy compared to mFOLFOX6/bev. Primary endpoint is progression-free survival (PFS) assessed by study investigator. Secondary endpoints include overall survival, objective response rate, safety profile, surgical conversion rate, disease control rate, duration of response, and PFS by retrospective central review. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; tumor determined to be dMMR by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2); availability of archived tumor tissue for central confirmation of dMMR status; and measurable disease per RECIST. Activated 11-7-17. As of 9-24-18, 13/347 pts have been enrolled. Clinical trial: NCT02997228. Support: U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; and Genentech, Inc. Clinical trial information: NCT02997228. </jats:p>