Single Arm Study of Neoadjuvant Dostarlimab in Stage II and III Deficient Mismatch Repair Colon Cancers

Inclusion Criteria:

• Capable of understanding and complying with the protocol requirements and havesigned the informed consent document. Patients with mild cognitive impairment may beconsidered for enrollment in the study if their legally authorized representativeprovides written informed consent for the patient.

• 18 years or older in age

• Biopsy proven dMMR (by IHC), Stage II or III colon cancer per CT imaging correlationwith AJCC 8th edition, 2017, amendable to en block surgical resection as determinedby colorectal surgeon.

• Biopsy specimen for diagnosis of dMMR Colon cancer should have enough tissue forminimum 4 and max 6 adjacent unstained FFPE slides (4µm each) as determined byProtocol Pathologist Dr. Anthony Snow for CD3+ and CD8+ analysis. If there is notenough tissue present in original sample, a repeat colonoscopy and biopsy may beperformed; otherwise patient is not eligible.

• Potentially surgically resectable Stage II or III patients who are willing to forgosurgical resection if study endpoints are met. Patient with easily manageable bowelchanges amenable to laxatives or stool softeners as outpatient per assessment bycolorectal surgery are allowed. (See exclusion criteria #2)

• ECOG performance status less than or equal to 1

• Absence of metastatic disease on CT CAP with Contrast within 28 days from treatmentstart

• Absolute neutrophil count greater than or equal to 1,500/µL

• Platelets greater than or equal to 100,000/µL

• Hemoglobin greater than or equal to 9 g/dL

• Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) orcalculated creatinine clearance 60mL/min using the Cockcroft-Gault equation

• Total bilirubin less than or equal to 1.5 x ULN (less than or equal to 2.0 inpatients with known Gilberts syndrome) OR direct bilirubin less than or equal to 1 xULN

• Aspartate aminotransferase and alanine aminotransferase less than or equal to 3.0 xULN

• International normalized ratio (INR) or prothrombin time (PT) less than or equal to 1.5× ULN unless patient is receiving anticoagulant therapy if PT or partialthromboplastin (PTT) is within therapeutic range of intended use of anticoagulants.Activated partial thromboplastin time (aPTT) less than or equal to 1.5× ULN unlesspatient is receiving anticoagulant therapy if PT or PTT is within therapeutic rangeof intended use of anticoagulants

• Participants of childbearing potential must have a negative serum pregnancy testwithin 72 hours prior to taking study treatment and agree to use an adequate methodof contraception from screening through 180 days after the last dose of studytreatment. Information must be captured appropriately within the site's sourcedocuments. Note: Abstinence is acceptable if this is the established and preferredcontraception for the patient.

• For males of reproductive potential: use of condoms or other methods to ensureeffective contraception with partner starting with first dose of study treatmentthrough 180 days after the last dose of study treatment. Note: Abstinence isacceptable if this is the established and preferred contraception for the patient.

Exclusion Criteria:

• Synchronous primary tumor (i.e. more than 1)

• Obstruction or perforation requiring diverting ostomy or immediate resection, orbright red blood per rectum requiring urgent blood transfusion, from their primarytumor.

• Clinical T4b tumors

• Known hypersensitivity to dostarlimab components or excipients.

• Major surgery less than or equal to 3 weeks prior to initiating protocol therapy

• Received investigational therapy less than or equal to 3 months, or within a timeinterval less than at least 5 half- lives of the investigational agent, whichever isshorter, prior initiating protocol therapy.

• Heavy bleeding from the colon cancer tumors requiring PRBC transfusions that wouldrequire palliative surgical resection

• Concurrent, clinically significant, active malignancies within two years of studyenrollment.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith 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 immunosuppressivedrugs). Other than Replacement hormone therapy with thyroxine for hypothyroidism ,insulin for T1 diabetes mellitus , or physiologic corticosteroid replacement therapyfor adrenal or pituitary insufficiency, etc.)

• Diagnosis of immunodeficiency or has received any systemic glucocorticoid therapy orany other form of immunosuppressive therapy within 7 days prior to initiatingprotocol therapy.

• History of greater than or equal to Grade 3 immune-related AE with priorimmunotherapy, except for non-clinically significant lab abnormalities.

• Patients with known HIV (Human Immunodeficiency Virus) infection on effectiveretroviral therapy regardless of CD4 count who have had an opportunistic infectionwithin the past 12 months.

• Organ transplant recipients on immunosuppressive medications

• Patients with chronic HBV infection with active disease who meet the criteria foranti HBV therapy but not on suppressive antiviral therapy prior to initiation oftreatment of this protocol are excluded. Also, patients with history of HCVinfection that have not completed curative antiviral treatment and the HCV viralload is not below the limit of quantification areexcluded.(e.g. a patient who is HCVAb positive but HCV RNA negative due to prior treatment or natural resolution iseligible.)

• 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

19. Patients with severe cognitive impairment.