Dostarlimab for Locally Advanced or Metastatic Cancer (Non-colorectal/Non-endometrial) With Tumor dMMR/MSI

Exclusion Criteria

• •1. Colorectal and endometrial cancer and all primary tumor not listed in inclusion criterion #4.
• •2. Previous exposure to anti-PD-1 or PD-L1 or anti-CTL-4 antibodies or treatment with immunotherapy.
• •3. Previous exposure to any investigational drug within 4 weeks (6 weeks for monoclonal antibodies) before the first dose in the study.
• •4. Previous exposure to any systemic anti-cancer therapy or radiation therapy for the cancer for which the patient is being enrolled.
• •5. Active autoimmune disease: Active autoimmune disease requiring systemic treatment in the past 2 years (excluding replacement therapy) or any history of interstitial lung disease (patients with ancient auto-immune disease with stable endocrine oral substitution are eligible).
• •6. Uncontrolled central nervous system metastases or carcinomatous meningitis or other concurrent illness or ongoing or active infections.
• •7. Patients with HER2-positive gastric carcinoma.
• •8. Other serious and uncontrolled non-malignant disease or is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• •9. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• •10. Has received treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to the first dose of adjuvant treatment or is required to receive systemic immunosuppressive medications during the study. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• •Note 1: Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled into the study after approval of the Medical Contact.
• •Note 2: patients are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses including doses \>10 mg daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is permitted.
• •11. Other concomitant or previous malignancy other than the disease under study, except as noted below:
• •i. adequately treated in-situ carcinoma of the uterine cervix, ii. basal or squamous cell carcinoma of the skin, iii. cancer from which the patients was in complete remission for \>2 years.
• •12. Known Human Immunodeficiency Virus (HIV) infection.
• •13. Received live vaccine within 14 days.
• •14. Patient has documented presence of HBsAg \[or HBcAb\] at pre-inclusion visit or within 3 months prior to first dose of study intervention.
• •Participant has a positive hepatitis C virus (HCV) antibody test result at pre-inclusion visit 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.
• •Participant has a positive HCV RNA test result at pre-inclusion visit 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
• •15. Known prior severe hypersensitivity to investigational product or any component in its formulation.
• •16. Pregnant or breast feeding women.
• •17. Participation in another clinical trial within 30 days prior to the first study treatment administration or concomitantly with the trial.
• •18. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• •19. Person deprived of their liberty or under protective custody or guardianship.
• •Patient randomized to receive SOC (Arm B) may crossover to receive dostarlimab (Arm A) in case of documented progressive disease according to RECIST v1.1.