Title
Phase II, Single Arm Study of Neoadjuvant Dostarlimab (TSR-042) in Stage II and III Deficient Mismatch Repair Colon Cancers

Description
Phase II, Single Arm Study of Neoadjuvant Dostarlimab (TSR-042) in Stage II and III Deficient Mismatch Repair Colon Cancers

Objective
The purpose of this research study is to look at the effects of the immunotherapy drug dostarlimab on dMMR colon cancer tumors and to see if these patients can avoid surgical resection, with the option to go to surgery only if the tumor does not respond.

Treatment This is a Phase II, single arm study looking at the rate of major clinical response and non-operative management in Stage II and III colon cancer after 18 weeks (up to 6 cycles) of neoadjuvant dostarlimab.

Key Eligibility Inclusion Criteria:

-Capable of understanding and complying with the protocol requirements and have signed the informed consent document. Patients with mild cognitive impairment may be considered for enrollment in the study if their legally authorized representative provides 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 correlation with 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 max 6 adjacent unstained FFPE slides (4µm 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 easily manageable bowel changes amenable to laxatives or stool softeners as outpatient per assessment by colorectal 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 treatment start
-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) or calculated 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 in patients with known Gilberts syndrome) OR direct bilirubin less than or equal to 1 x ULN
-Aspartate aminotransferase and alanine aminotransferase less than or equal to 3.0 x ULN
-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 partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) less than or equal to 1.5× 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.

Applicable Disease Sites
Colon and Rectum

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital