Immunotherapy (Dostarlimab) for the Treatment of Stage II and III Deficient Mismatch Repair Colon Cancer

Inclusion Criteria

• Patient or their legally authorized representative (LAR) capable of understanding and complying with the protocol requirements and they or their LAR have signed the informed consent document
• 18 years or older in age
• Biopsy proven dMMR (by immunohistochemistry [IHC]), stage II or III colon cancer per imaging correlation with American Joint Committee on Cancer [AJCC] 8th edition, 2017, amendable to en block surgical resection as determined by colorectal surgeon
• Biopsy specimen for diagnosis of dMMR colon cancer should have enough tissue for minimum 4 and maximum 6 adjacent unstained formalin-fixed paraffin-embedded (FFPE) slides (4um each) as determined by protocol pathologist Dr. Anthony Snow for CD3+ and CD8+ analysis. If there is not enough tissue present in original sample, a repeat colonoscopy and biopsy may be performed otherwise patient is not eligible
• Potentially surgically resectable, stage II or III patients who are willing to forgo surgical resection if study endpoints are met. Patient with bowel changes amenable to laxatives or stool softeners as outpatient per assessment by colorectal surgery are allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Absence of metastatic disease on imaging with contrast within 28 days from treatment start
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 60 mL/min using the Cockcroft-Gault equation
• Total bilirubin =< 1.5 x ULN (=< 2.0 in patients with known Gilberts syndrome) OR direct bilirubin =< 1 x ULN
• Aspartate aminotransferase and alanine aminotransferase =< 3.0 x ULN
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy if PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants
• Participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to taking study treatment and agree to use an adequate method of contraception from screening through 180 days after the last dose of study treatment. Information must be captured appropriately within the site’s source documents. * Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner starting with first dose of study treatment through 180 days after the last dose of study treatment * Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Exclusion Criteria

• Synchronous primary tumor (i.e. more than 1)
• Obstruction or perforation requiring diverting ostomy or immediate resection, or bright red blood per rectum requiring urgent blood transfusion, from their primary tumor
• Clinical T4b tumors
• Known hypersensitivity to dostarlimab components or excipients
• Major surgery =< 3 weeks prior to initiating protocol therapy
• Received investigational therapy =< 3 months, or within a time interval less than at least 5 half lives of the investigational agent, whichever is shorter, prior initiating protocol therapy
• Heavy bleeding from the colon cancer tumors requiring packed red blood cell transfusion (PRBC) transfusions that would require palliative surgical resection
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, glucocorticoids, or immunosuppressive drugs). Other than replacement hormone therapy with thyroxine for hypothyroidism, insulin for type 1 (T1) diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.
• Diagnosis of immunodeficiency or has received any systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy
• History of >= grade 3 immune-related adverse event (AE) with prior immunotherapy, except for non-clinically significant lab abnormalities
• Patients with known HIV (human immunodeficiency virus) infection on effective retroviral therapy regardless of CD4 count who have had an opportunistic infection within the past 12 months
• Patients with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti HBV therapy but not on suppressive antiviral therapy prior to initiation of treatment of this protocol are excluded. Also, patients with history of hepatitis C virus (HCV) infection that have not completed curative antiviral treatment and the HCV viral load is not below the limit of quantification are excluded. (e.g. a patient who is HCV Ab positive but HCV ribonucleic acid [RNA] negative due to prior treatment or natural resolution is eligible)
• Prior history of interstitial lung disease
• Received a live vaccine within 30 days of initiating protocol therapy
• Not enough tissue for confirming dMMR status and CD3+ /CD8+ testing