Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study: A Randomized Phase III Study of mFOLFOX6/Bevacizumab Combination Chemotherapy with or without Atezolizumab or Atezolizumab Monotherapy in the First-Line Treatment of Patients with Deficient DNA Mismatch Repair (dMMR) Metastatic Colorectal Cancer
Objective
Primary Objective:
- To determine the efficacy, based on PFS, of mFOLFOX6/bevacizumab plus atezolizumab (combination) and atezolizumab (single agent) as compared to mFOLFOX6/bevacizumab (control).
Secondary Objectives:
- To compare the overall survival.
- To compare the objective response rates (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- To determine the safety profiles of the combination of mFOLFOX6/bevacizumab/atezolizumab and atezolizumab monotherapy in patients with mismatch-repair deficient (dMMR) metastatic colorectal cancer (mCRC).
- To compare the surgical conversion rate.
- To compare disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 12 months.
- To determine the duration of response and stable disease. VII. To determine the progression-free survival (PFS) by retrospective central independent scan review.
Study Arms
- Active Comparator: Arm I (bevacizumab, mFOLFOX6)
- Experimental: Arm II (atezolizumab)
- Experimental: Arm III (atezolizumab, bevacizumab, mFOLFOX6)
Eligibility
- Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer
- Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; Note: microsatellite instability high (MSI-H) diagnosed by microsatellite instability (MSI) testing (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) is not eligible unless dMMR is confirmed by CLIA-certified immunohistochemical (IHC) assay with a panel of all four IHC markers including MLH1, MSH2, PMS2 and MSH6
- An adequate amount of archived tumor tissue, either from primary colorectal cancer site or metastatic lesions
- Documentation by positron emission tomography(PET)/computed tomography (CT) scan, CT scan, or magnetic resonance imaging (MRI) that the patient has untreated measurable metastatic disease per RECIST 1.1
- No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass
- Absolute neutrophil count (ANC) must be >= 1500/mm^3 (obtained within 28 days prior randomization)
- Platelet count must be >= 100,000/mm^3 (obtained within 28 days prior randomization)
- Hemoglobin must be >= 8 g/dL (obtained within 28 days prior randomization)
