Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy of perioperative dostarlimab compared with standard of care (SOC) in participants with untreated T4N0 or Stage III (resectable), defective mismatch repair/ microsatellite instability high (dMMR/MSI-H) colon cancer.

Official Title
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A Phase 3, Open-Label, Randomized Study of Perioperative Dostarlimab Monotherapy Versus Standard of Care in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer

Conditions
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Colonic Neoplasms, Neoplasms, Colon

Intervention / Treatment
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* Biological: Dostarlimab
* Drug: CAPEOX
* Drug: FOLFOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has untreated pathologically confirmed colon adenocarcinoma Has resectable colon adenocarcinoma defined as clinically T4N0 or Stage III Has radiologically evaluable disease Has a tumor demonstrating the presence of either dMMR status or MSI-H Exclusion Criteria: Has distant metastatic disease. Has received prior medical therapy (chemotherapy, immunotherapy, biologic, or targeted therapy), radiation therapy or surgery for management of colon cancer Has a tumor that, in the investigator's judgment is causing symptomatic bowel obstruction or otherwise requires urgent/emergent surgery Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury within 28 days prior to enrollment Has any history of interstitial lung disease or pneumonitis Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice Has a history of allogenic stem cell transplantation or organ transplantation Is receiving any other anticancer or experimental therapy. No other experimental therapies (including but not limited to chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, or other experimental drugs) of any kind are permitted while the participant is receiving study intervention Is pregnant, breastfeeding, or expecting to conceive children within the projected duration of the study Has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or known allergies to dostarlimab, or its excipients, or any components of FOLFOX or CAPEOX

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dostarlimab<br>Participants will receive Dostarlimab pre and post surgery | Biological: Dostarlimab<br>* Dostarlimab will be administered.<br>|
| Active Comparator: Standard of Care (SOC)<br>Participants will receive SOC (FOLFOX/CAPEOX) or undergo expectant observation post surgery. | Drug: CAPEOX<br>* CAPEOX will be administered.<br>Drug: FOLFOX<br>* FOLFOX will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival (EFS) Assessed by Blinded Independent Central Review (BICR) | EFS is defined as the time from randomization to either disease recurrence or death due to any cause or treatment related toxicity that results in the participant not being suitable for surgery | Up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Pathological Response | Pathological response will be categorized as a complete pathologic response, major pathologic response, partial pathologic response, or negligible pathologic response. | Up to approximately 5 years | 
| Overall Survival (OS) | OS is defined as time from randomization to death from any cause | Up to approximately 5 years | 
| Event-free Survival (EFS) assessed by local assessment | EFS is defined as the time from randomization to either disease recurrence or death due to any cause or treatment related toxicity that results in the participant not being suitable for surgery | Up to approximately 5 years | 
| Number of Participants with treatment emergent adverse events (AEs), serious adverse events (SAEs), Immune-related Adverse Event (irAEs), AEs leading to death and AEs leading to discontinuation of study treatment |  | Up to approximately 5 years | 
| Number of Participants with AEs and SAEs by Severity |  | Up to approximately 5 years | 
| Serum Concentration of Dostarlimab |  | Predose and End of Infusion (EoI) of Cycle 1 and EoI of Cycle 2 to Cycle 10 (each cycle is of 21 days) | 
| Serum Concentration of Dostarlimab at End of Infusion (C-EoI) |  | End of Infusion (EoI) of Cycle 1 to Cycle 10 (each cycle is of 21 days) | 
| Serum Predose trough concentration (Ctrough) of Dostarlimab |  | Predose of Cycle 1 to Cycle 10 (each cycle is of 21 days) | 
| Number of Participants with Anti-Drug Antibodies against Dostarlimab |  | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JEMPERLI, Dostarlimab, dostarlimab-gxly, TSR-042, GSK4057190A, FOLFOX, CAPEOX, Colon Cancer, Resectable colon cancer, dMMR/MSI, Perioperative, Neoadjuvant, Adjuvant