A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors

This is a multicenter, prospective open-labeled phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of Regorafenib given in combination with Avelumab (no dose escalation for Avelumab) in patients with advanced digestive solid tumors followed by independent phase II trials to evaluate the association of Regorafenib at the RP2D with Avelumab in 17cohorts of advanced or metastatic tumors : * Cohort A: Colorectal cancer not MSI-H or MMR-deficient * Cohort B: GIST * Cohort C: Oesophageal or gastric carcinoma * Cohort D: Biliary tract cancer, hepatocellular carcinoma * Cohort E: Soft-tissue sarcoma (STS) * Cohort F: Radioiodine-refractory differentiated thyroid cancer (RR-DTC) * Cohort G: Neuroendocrine gastroenteropancreatic tumors (GEP-NETs) * Cohort H: Non-small cell lung cancer (NSCLC) * Cohort I: Solid tumors (including soft-tissue sarcoma) with immune signature (TLS+). In addition, to evaluate in a phase II trial, the association of a low-dose of regorafenib (80mg/day) with avelumab : * Cohort A': colorectal not MSI-H or MMR-deficient (low dose) * Cohort J: urothelial cancer * cohort K: HPV-associated cancer with molecular confirmation p16 positive status * cohort L: triple netagtive brest cancer * cohort M: TMH-high solid tumors with status TMB-high already known * cohort N: MSI-high solid tumors with status MSI-high already known * cohort O: non clear-cell renal carcinoma * cohort P: malignant pleural mesothelioma