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): Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) study (NRG-GI004/SWOG-S1610).

Authors

Caio Max Rocha Lima

Caio Max Sao Pedro Rocha Lima

NRG Oncology and Wake Forest University Baptist Medical Center, Winston-Salem, NC

Caio Max Sao Pedro Rocha Lima , Greg Yothers , Samuel A. Jacobs , Hanna Kelly Sanoff , Deirdre Jill Cohen , Katherine A Guthrie , Norah Lynn Henry , Patricia A. Ganz , Scott Kopetz , Peter C. Lucas , Charles David Blanke , Norman Wolmark , Howard S. Hochster , Thomas J. George , Michael J. Overman

Organizations

NRG Oncology and Wake Forest University Baptist Medical Center, Winston-Salem, NC, NRG Oncology, and The University of Pittsburgh, Pittsburgh, PA, NRG Oncology, and the University of Pittsburgh, Pittsburgh, PA, NRG Oncology, UNC Lineberger Comprehensive Cancer Center, and The Alliance for Clinical Trials in Oncology, Chapel Hill, NC, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, and ECOG-ACRIN, New York, NY, Fred Hutchinson Cancer Research Center, and SWOG Statistics and Data Management Center, Seattle, WA, University of Michigan Rogel Cancer Center, and SWOG, Ann Arbor, MI, NRG Oncology, and The UCLA Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, MD Anderson Cancer Center and SWOG, Houston, TX, NRG Oncology, and University of Pittsburgh School of Medicine, Pittsburgh, PA, OHSU School of Medicine and SWOG, Portland, OR, Rutgers Cancer Institute, New Brunswick, NJ, NRG Oncology, and The University of Florida Health Cancer Center, Gainesville, FL, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health, Pharmaceutical/Biotech Company

Background: Deficient DNA mismatch repair (dMMR) colorectal cancer (CRC) is highly immunogenic. Preclinical data showed synergistic interactions among FOLFOX, anti-VEGF, and programmed cell death-1 (PD-1) pathway blockade. Prior phase I study of mFOLFOX6/ bevacizumab (bev) + atezolizumab (atezo) was well tolerated and enhanced intratumoral infiltration of CD8+ T cells. We hypothesize that the dMMR subset of CRC may be effectively targeted with combination of PD-1 pathway blockade and mFOLFOX6/bev. Methods: This is a prospective randomized phase III open-label trial. Pts (N=347) with mCRC dMMR will be randomized to three 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 endpoint is progression-free survival (PFS) assessed by study investigator of mFOLFOX6/bev/atezo and atezo monotherapy compared to mFOLFOX6/bev. Secondary endpoints include OS, objective response rate, safety profile, 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; dMMR tumor determined 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 9-11-19, enrollment continues with 44/347 pts enrolled. Clinical trial: NCT02997228. Support:U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228

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Abstract Details

Meeting

2020 Gastrointestinal Cancers Symposium

Session Type

Trials in Progress Poster Session

Session Title

Trials in Progress Poster Session C: Anal and Colorectal Cancer

Track

Colorectal Cancer,Anal Cancer

Sub Track

Therapeutics

Clinical Trial Registration Number

NCT02997228

Citation

J Clin Oncol 38, 2020 (suppl 4; abstr TPS260)

Abstract #

TPS260

Poster Bd #

M16

Abstract Disclosures

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