Chemotherapy, Bevacizumab, and/or Atezolizumab for Patients With Deficient DNA Mismatch Repair (dMMR or MSI-H) Metastatic Colorectal Cancer, the COMMIT Study

About the Study

This study is for people with metastatic colorectal cancer. The study will compare how well treatment with a combination of chemotherapy agents and an immunotherapy agent works compared with treatment using an immunotherapy agent alone. This study is focused on patients who are determined to be mismatch-repair deficient (dMMR) or have an MSI-H diagnosis, which are commonly seen in people with Lynch syndrome.

Type of Study

The study is an open-label, Phase III, randomized study.  

There are two remaining treatment groups in this study. One group will receive combination chemotherapy along with the immunotherapy drug atezolizumab.  The other group will receive immunotherapy drug atezolizumab alone. (A third study group who were to receive combination chemotherapy alone is no longer accepting new patients.) 

The study is randomized; participants will be placed into one of the two study groups by chance.

The study is open-label. All participating patients will know which of the two groups they have been assigned to and which treatments they are being given.

What the Study Entails

Patients will be assigned randomly to either Group 2 or Group 3.

• Group 1: Chemotherapy Only - This study group is closed
• Group 2: Immunotherapy Only
  • Patients receive the immunotherapy atezolizumab IV over 30-60 minutes on day 1.
  • Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity.
• Group 3: Chemotherapy and Immunotherapy
  • Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity.
  • Patients also receive combination chemotherapy intravenously (bevacizumab oxaliplatin, leucovorin calcium and fluorouracil) starting on day 1.  Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity.  Cycles of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks for 18 months, and then every 12 weeks for up to 5 years.

Men or women age 18 years or older can participate if they:  

• Have metastatic colon or rectal cancer without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer
• Tumor determined to be mismatch-repair deficient (dMMR); patients with MSI-H diagnosis are also eligible
• Have no immediate need for surgical intervention

Patients will be excluded if they:  

• Have central nervous system (CNS) metastases (Contact the study team to review a list of exceptions)
• Have uncontrolled high blood pressure
• Have a severe cardiac condition
• Have a serious or non-healing wound, skin ulcer, or bone fracture
• Have a history of transient ischemic attack (TIA), cerebrovascular accident (CVA), gastrointestinal (GI) perforation or blood clot within 6 months prior to study enrollment
• Have had prior treatment with anti-PD-1 or anti-PD-L1 therapy (also known as immune check point inhibitors)
• Have clinically significant liver disease
• Have a history or risk of autoimmune disease (Contact the study team to review a list of exceptions)
• Have a history of lung tissue inflammation or lung disease
• Have known active tuberculosis (TB)
• Women who are pregnant