• Patient must have signed a written informed consent form prior any trial specific procedures. -

• 18 years or older patients.

• Documented locally advanced or metastatic disease with no previous systemic anti-cancer treatment in these settings and not suitable for complete surgical resection.

• Histologically proven, dMMR/MSI-H solid tumors that are not colorectal or endometrial cancers and including one of the following: duodenum and small bowel adenocarcinoma, gastric and oeso-gastric junction adenocarcinoma with CPS\<5, pancreatic adenocarcinoma, ampulla of Vater adenocarcinoma, adrenocortical carcinoma, carcinoma of unknown primary site, neuroendocrine carcinoma (Grade 3) all primary, and soft tissue sarcoma except Gastro-Intestinal Stromal Tumor (GIST).

• If patient received adjuvant therapy for non-metastatic disease, this therapy should be completed more than 6 months before the diagnosis of metastatic or recurrent disease.

• Availability of minimum 1 block of tumor tissue or 20 slides (archival (\<2 years) or fresh biopsy specimen of primary and or metastasis) for centralized confirmation of MMR/MSI status by IHC or NGS/PCR, and for Translational Research.

• Patients with dMMR/MSI tumor analyzed by IHC, PCR (for Gastric and OGJ adenocarcinoma, and duodenum and small bowel adenocarcinoma only), and/or NGS at the recruiting center should be confirmed by central review within 24h (every anonymized patient analysis reporting will be provided for central review). Patients should not be included in the study until the dMMR/MSI status is confirmed by the review committee.

• NB: In case of ambiguous result of IHC (lack of positive internal control, heterogeneous loss of MMR protein expression, ambiguous loss of only one protein including HMSH6 and PMS2), the MSI-H status will be assessed by PCR or NGS for gastric and OGJ adenocarcinoma, and duodenum and small bowel adenocarcinoma, and by NGS for other primary. Based on IHC and PCR or NGS results (NGS will be centrally performed in this case ), the sponsor will decide if inclusion is possible;

• Presence of at least one measurable lesion within 28 days before the start of treatment according to RECIST v1.1.

• Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1.

⁃ Haematological status: absolute neutrophil count (ANC) ≥1.5 x 10⁹/L; platelets ≥100 x 10⁹/L; haemoglobin ≥9 g/dL.

⁃ Adequate renal function: serum creatinine level \<120 µM, or clearance \>50 ml/min (Modification of the Diet in Renal Disease \[MDRD\] or Cockcroft and Gault).

⁃ Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless liver metastases are present, in which case they must be ≤ 5× ULN.

⁃ For patients not taking warfarin: International normalised ratio (INR) \<1.5 or prothrombin time (PT) \<1.5 x ULN and either partial thromboplastin time (PTT) or activated PTT (aPTT) \<1.5 x ULN. Participants taking warfarin may be included on a stable dose with a therapeutic INR \<3.5.

⁃ Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours before the date of randomization.

⁃ Men, and women of childbearing potential must agree to use adequate contraception for the duration of trial participation and for 4 months after the last dose of dostarlimab (used in first line or at crossover) or for at least 6 months after the last administration of the chemotherapy agent(s) used in the control arm if no crossover with dostarlimab (according to the current version of the summary of product characteristics (SmPC) of each chemotherapy agent). Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.

⁃ Registration in a National Health Care System.

⁃ Patient is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.