Study on the Effectiveness and Safety of the Combination of the Two Drugs Regorafenib and Nivolumab in Patients With Colorectal Cancer (Cancer of the Colon or Rectum Classified as Proficient Mismatch Repair and Microsatellite Stable)
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Regorafenib (Stivarga, BAY73-4506); Nivolumab (Opdivo)
Intervention description: Regorafenib administered as oral tablets given every day for 3 weeks of each 28 days treatment cycle (i.e., 3 weeks on, 1 week off); Administered on day 1 of every treatment cycle.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to learn if combination of the two drugs regorafenib and
      nivolumab is an effective treatment for pMMR - MSS colorectal cancer, a special type of
      cancer of the colon or rectum (pMMR stands for proficient Mismatch Repair; MSS stands for
      Microsatellite Stable) and whether it is safe for patients. Regorafenib works by blocking
      several different proteins involved in tumor growth. Nivolumab is an immunotherapy drug
      encouraging the body's own immune system to attack cancer cells.

      Both drugs have been approved, but not for how they are being used as combination therapy in
      this study. Brand name of regorafenib is Stivarga; brand name of nivolumab is Opdivo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological confirmed advanced, metastatic, or progressive pMMR/MSS
             adenocarcinoma of colon or rectum

          -  Participant must have progressed or be intolerant to prior systemic chemotherapy
             including fluoropyrimidines, irinotecan, oxaliplatin, anti-vascular endothelial growth
             factor (VEGF) therapy, and, if extended rat sarcoma viral oncogene homolog (RAS) wild
             type, an anti-epidermal growth factor receptor (EGFR) therapy. Exceptions may apply

          -  Participants must have adequate organ and marrow function defined by
             protocol-specified laboratory tests

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  Measurable disease as determined by response evaluation criteria in solid tumors
             (RECIST) v1.1

          -  Provision of recently obtained tumor tissue as per protocol specified requirement

          -  Anticipated life expectancy greater than 3 months

          -  Be able to swallow and absorb oral tablets

        Exclusion Criteria:

          -  Participants with Mismatch repair deficient (dMMR) / microsatellite instable-high
             (MSI-H) colorectal cancer

          -  Prior therapy with regorafenib, anti-programmed cell death protein 1 (PD-1),
             programmed cell death protein 1 ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated
             protein 4 (CTLA-4) inhibitors, or any form of immunotherapy to treat cancer

          -  Presence of active central nervous system (CNS) metastases; participants with stable
             CNS disease or previously treated lesions are eligible for study entry

          -  Poorly controlled hypertension, defined as a blood pressure consistently above 150/90
             mmHg despite optimal medical management

          -  Arterial thrombotic or embolic events such as cerebrovascular accident (including
             transient ischemic attacks) within 6 months before the start of study medication.
             Active pulmonary emboli or deep vein thrombosis that are significant or not adequately
             controlled on anticoagulation regimen

          -  Any hemorrhage or bleeding event ≥ National Cancer Institute - Common terminology
             criteria for adverse events (NCI-CTCAE) Grade 3 within 28 days prior to the start of
             study medication

          -  Participants with an active, known or suspected autoimmune disease

          -  History of interstitial lung disease or pneumonitis

          -  Known history of human immunodeficiency virus (HIV) infection or current chronic or
             active hepatitis B or C infection

          -  Other protocol defined inclusion/exclusion criteria could apply