PRODIGE 90 - (FFCD 2204) Neoadjuvant Dostarlimab with Short Course Radiotherapy in a Watch-and-wait Strategy for Microsatellite Unstable or Mismatch Repair-deficient Locally Advanced Rectal Cancer Patients

Inclusion Criteria: * Age ≥18 years * Histologically proven rectal adenocarcinoma with Mismatch-repair Deficient (dMMR)/ microsatellite instability-high (MSI-H). Tumour status (dMMR/MSI-H) should be determined using both IHC (Immunohistochemistry) and PCR (polymerase chain reaction) or NGS (Next-Generation sequencing) * Stage II or III and middle and lower third rectal adenocarcinoma (diagnosed on the basis of standard clinical and MRI criteria) * WHO performance status 0 or 1 * Adequate liver function: AST and ALT ≤ 5 x ULN (upper normal limit), total bilirubin ≤ 35 μM/L, albumin ≥ 28 g/L and Child-Pugh A score (if cirrhosis associated) * Adequate hematological and renal function (hemoglobin \> 9 g/dl, platelets \> 100 G/L, ANC ≥ 1.5 G/L) and renal function (creatinine clearance ≥ 40ml/min according to MDRD formula) * Women of childbearing potential must agree to use contraception during the trial treatment and for at least 4 months after discontinuation of the experimental treatments. Men who have sex with women of childbearing potential must agree to use contraception during treatment and for at least 4 months after discontinuation of the experimental treatments * Ability of patient to understand, sign and date the informed consent form before any study specific screening procedures * Patient affiliated to a social security scheme Exclusion Criteria: * Stage IV and upper third rectal adenocarcinoma (above 10 cm from the anal verge or sus-peritoneal on standard clinical and MRI criteria) * Patients who have already received immunotherapy, chemotherapy or radiotherapy for rectal cancer * Persistent toxicities related to prior treatment of grade greater than 1 * Participant has an active infection requiring systemic therapy within 1 week prior to the anticipated first dose of study treatment * Contraindication to pelvic radiotherapy * Hypersensitivity to dostarlimab or any of its excipients * Allergy to any component of Chinese hamster ovary cells * History of severe active life-threatening autoimmune disease * History of uncontrolled or symptomatic cardiac disease. * Interstitial lung disease * Uncontrolled central nervous system metastases or carcinomatous meningitis * Patient has documented presence of HBsAg \[or HBcAb\] at screening or within 3 months prior to first dose of study intervention * Patient has a positive HCV antibody test result at screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled, only if a confirmatory negative HCV RNA test is obtained * Patient has a positive HCV RNA test result at Screening or within 3 months prior to first dose of study intervention. NOTE: The HCV RNA test is optional and participants with negative HCV antibody test are not required to undergo HCV RNA testing as well * Known HIV infection * Vaccinations (live vaccine) within 14 days prior to start of treatment * Immunosuppression, including subjects with conditions requiring systemic corticosteroid treatment (\>10 mg/day prednisone equivalent) * Active autoimmune disease requiring systemic treatment (vitiligo excluded) in the past 2 years or recent receipt within the previous 7 days of immunosuppressive therapy * History of organ transplantation * Pregnant or breastfeeding women * Patient has experienced any of the following with prior immunotherapy: any immune-related AE (irAE) of Grade 3 or higher, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms \[DRESS\] syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary * Any progressive disease that has not been balanced over the last 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency, etc * Other cancer treated within the last 5 years except in situ cervical carcinoma or basocellular/ spinocellular carcinoma or a cancer of the lynch syndrome spectrum considered cured at the time of inclusion * Major surgery within 4 weeks before inclusion * Persons deprived of liberty or under guardianship or incapable of giving consent * Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol or follow-up schedule