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Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study: A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC)—NRG-GI004/SWOG-S1610
- Source :
- Journal of Clinical Oncology. 39:TPS3618-TPS3618
- Publication Year :
- 2021
- Publisher :
- American Society of Clinical Oncology (ASCO), 2021.
-
Abstract
- TPS3618 Background: The superiority of inhibition of programmed cell death-1 (PD-1) pathway in dMMR/MSI-H over chemotherapy with either anti-vascular endothelial growth factor receptor (VEGFr) or anti- epithelial growth factor receptor (EGFr) antibodies in mCRC has been demonstrated in a phase III trial (N Engl J Med 2020; 383:2207). However, more patients had progressive disease as the best response in the anti-PD1 monotherapy arm (29.4% vs. 12.3%) with mean progression-free survival (PFS) of 13.7 months. Preclinical models have demonstrated synergistic interactions between FOLFOX, anti-VEGF, and anti-PD-1. We hypothesize that the dMMR/MSI-H mCRC patients may be more effectively treated by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-L1 therapy (atezo) alone. Methods: Initially a three-arm study, the mFOLFOX6/bev arm was closed to new enrollment on 6-4-20 due to emerging data; the redesigned COMMIT trial was reactivated on 1/29/2021 as a prospective phase III open-label trial that randomizes (1:1) mCRC dMMR/MSI-H pts (N=211) to either atezo monotherapy or mFOLFOX6/bev+atezo combination. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is PFS as assessed by site investigator. Secondary endpoints include overall survival (OS), objective response rate (RECIST v1.1), safety profile, disease control rate, duration of response, and centrally-reviewed PFS. 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) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Clinical trial: NCT02997228. Support: U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.
- Subjects :
- Oncology
Cancer Research
medicine.medical_specialty
Chemotherapy
Bevacizumab
business.industry
Colorectal cancer
medicine.medical_treatment
Cell
Microsatellite instability
medicine.disease
digestive system diseases
First line treatment
medicine.anatomical_structure
Atezolizumab
Internal medicine
medicine
DNA mismatch repair
business
medicine.drug
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi...........5bf7952ac31a031aad051b57fae4b6d4
- Full Text :
- https://doi.org/10.1200/jco.2021.39.15_suppl.tps3618