IMHOTEP

I1. Age ≥ 18 years on the day of signing informed consent.

I2. Histologically proven localized non-metastatic tumor included in one of the 4 cohorts:

• Colorectal Cancer (cT3/T4 N0 M0 ou cT N+ M0 on thoraco-abdomino-pelvic TAP CT-scan and echo-endoscopy) OR
• Oesogastric (gastric, gastro-oesophageal or oesophageal) cancer (cT2 to cT4 N M0 on TAP CT-scan and echo-endoscopy) OR
• Endometrial carcinoma (stage III) OR
• Other tumor types (cT2 to cT4 N M0 on TAP CT-scan and echo-endoscopy): biliary tract or pancreas adenocarcinoma, small bowel adenocarcinoma (duodenum, jejunum, ileum), peritoneum adenocarcinoma.

I3. MSI/dMMR established by immunohistochemistry (IHC) [MMR protein expression] and polymerase chain reaction (PCR) [both techniques are required] and validated by coordinator's team.

MMR and/or MSI tumors will be assessed using IHC with four antibodies (anti-MLH1, anti-MSH2, anti-MSH6 and anti-PMS2) and PCR (pentaplex panel is recommended: BAT-25, BAT-26, NR-21, NR-24, and NR-27) prior to screening. Loss of MLH1 and PMS2 / or MSH2 and MSH6 / or MSH6 alone / or PMS2 alone protein staining by IHC indicates dMMR, and tumor with ≥ 2 unstable markers among 5 microsatellite markers analyzed on PCR (BAT25, BAT26, NR21, NR24, and NR27) proves MSI/dMMR.

OR EBV-positive gastric cancers. EBV positivity will be assessed by EBER (EBV-encoded small RNAs) in situ hybridization (ISH) (EBER-PNA EnVision flex probe (Dako)). The intensity of staining (weak, moderate or intense) and the percentage of positive cells will be recorded. Cases showing nuclear staining in at least 5% of tumor cells will be considered positive for EBV infection.

I4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1 within 7 days prior to the inclusion.

I5. Adequate bone-marrow, hepatic, and renal functions, within 10 days prior to the start of study treatment with:

• Hemoglobin ≥ 9 g/dl or ≥ 5.6 mmol/l, neutrophils ≥ 1.0 x 10^9/l, platelets ≥ 100 x 10^9/l,
• Creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min/1.73m² using either MDRD or CKD-EPI formula,
• AST and ALT ≤ 3 x ULN, total bilirubin ≤ 1.5 ULN (or direct bilirubin ≤ ULN for patients with total bilirubin >1.5 × ULN),
• International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants.

I6. Covered by a medical/health insurance.

I7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

I8. Patients of childbearing potential accepting to use effective contraceptive measures or abstain from heterosexual activity, for the course of the study through 4 months after the last dose of pembrolizumab MK-3475 adjuvant treatment or 6 months after adjuvant chemotherapy or being surgically sterile. Refer to Appendix 1 for approved methods of contraception.

I9. Signed and dated IRB/IE approved informed consent form.