The goal of this open-label randomized, multicenter, comparative phase II trial is to evaluate the efficacy of the immunotherapy, dostarlimab, as first-line treatment for deficient mismatch repair (dMMR)/microsatellite instability (MSI) non-resectable metastatic or locally advanced non-colorectal and non-endometrial cancers compared to the standard of care chemotherapy.
Adult patients (aged ≥18 years) with histologically confirmed dMMR/MSI duodenum and small bowel adenocarcinoma, gastric and oeso-gastric junction (OGJ) adenocarcinoma with combined positive score (CPS)\<5, pancreatic adenocarcinoma, ampulla of vater adenocarcinoma, adrenocortical carcinoma, carcinoma of unknown primary site, neuroendocrine carcinoma (Grade3) all primary, and soft tissue sarcoma (except Gastro-Intestinal Stromal Tumor) will be included in this study. They will be randomized and treated with either dostarlimab (experimental arm A), or chemotherapy (control arm B).
Patients with documented disease progression following the first line chemotherapy (Arm B) may be eligible for crossover to be treated with dostarlimab, with the same schedule as arm A.
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).
Colorectal and endometrial cancer and all primary tumor not listed in inclusion criterion #4.
Previous exposure to anti-PD-1 or PD-L1 or anti-CTL-4 antibodies or treatment with immunotherapy.
Previous exposure to any investigational drug within 4 weeks (6 weeks for monoclonal antibodies) before the first dose in the study.
Previous exposure to any systemic anti-cancer therapy or radiation therapy for the cancer for which the patient is being enrolled.