Clinical Trials in Progress: COMMIT Study

Oncology, ONCOLOGY Vol 35, Issue 6,
Pages: 367

NRG-GI004/SWOG-S1610: Colorectal Cancer Metastatic dMMR/MSI-H Immunotherapy (COMMIT) Study: A Randomized Phase 3 Study of mFOLFOX6/Bevacizumab/Atezolizumab Combination vs Single Agent Atezolizumab in the First-Line Treatment of Patients With Deficient DNA Mismatch Repair (dMMR)/Microsatellite Instability–High (MSI-H) Metastatic Colorectal Cancer (NCT02997228).

Background

In metastatic colorectal cancer that is dMMR/MSI-H, the superiority of inhibition of the PD-1 pathway over chemotherapy with either anti-VEGFR or anti-EGFR antibodies has been demonstrated in a phase 3 trial.1 However, more patients had progressive disease as the best response in the anti–PD-1 monotherapy arm (29.4% vs 12.3%), with mean progression-free survival (PFS) of 13.7 months. Preclinical models have demonstrated synergistic interactions among folinic acid, fluorouracil, and oxaliplatin (FOLFOX); anti-VEGF; and anti–PD-1.

The primary objective of this study is to determine the efficacy of the combination of mFOLFOX6/bevacizumab (Avastin) plus atezolizumab (Tecentriq) as compared with single-agent atezolizumab, based on PFS. Secondary objectives include overall survival, objective response rate, duration of response, duration of stable disease, rate of PFS, and disease control rate (complete and partial responses and stable disease) at 12 months.

Selected inclusion criteria

Eligible patients must be 18 years or older with metastatic adenocarcinoma of the colon or rectum, without previous therapy for metastatic colorectal cancer; have an ECOG performance status of 0, 1, or 2; and have measurable metastatic disease and adequate organ function. Additionally, they must have their tumor determined to be dMMR by CLIA-certified immunohistochemical (IHC) assay with a panel of all 4 IHC markers, including MLH1, MSH2, PMS2, and MSH6; or, alternatively, MSI-H status diagnosed by polymerase chain reaction–based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing. Those with prior treatment with anti–PD-1 or anti–PD-L1 therapeutic antibody or pathway-targeting agents are excluded.

Patient accrual information

  • Reopen date: January 29, 2021
  • Accrual goal: 211 patients
  • Percent accrued: 28%

Study sites: NRG Oncology, SWOG, ECOG-ACRIN Cancer Research Group, and The Alliance for Clinical Trials in Oncology.

Reference

1. André T, Shiu K-K, Kim TW, et al; KEYNOTE-177 Investigators. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;
383(23):2207-2218. doi:10.1056/NEJMoa2017699

Contact Information: Coprincipal Investigators

Caio Max Sao Pedro Rocha Lima, MD, MS

Wake Forest University Baptist Health

One Medical Center Blvd

Winston-Salem, NC 27157

Phone: 336-713-5440

Email: crochali@wakehealth.edu

Michael Overman, MD

MD Anderson Cancer Center

1515 Holcombe Blvd, Unit 207

Houston, TX 77030

Phone: 713-745-4317

Email: moverman@mdanderson.org