Inclusion Criteria:

• Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+) locally advanced rectal adenocarcinoma.

• Has radiologically and endoscopically evaluable disease.

• Has a tumor demonstrating the presence of either:

  1. dMMR status; MMR status must be assessed by immunohistochemistry for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of 1 or more proteins indicates dMMR; MMR status will be determined locally; or
  2. MSI-H phenotype as determined by polymerase chain reaction or by tissue next generation sequencing; MSI-H will be determined locally.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Has adequate organ function.

Exclusion Criteria:

• Has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer.
• Has a tumor that, in the investigator's judgment, is causing symptomatic bowel obstruction or otherwise requires urgent/emergent local intervention. Participants with a history of bowel obstruction are eligible after obstruction is relieved by a diverting stoma (defunctioning colostomy). Patients with a history of bowel obstruction in the context of current rectal cancer diagnosis and treated with stenting are not eligible.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury within 28 days prior to enrollment.
• Is receiving any other anticancer or experimental therapy.