IMMUNORARE5: A National Platform of 5 Academic Phase II Trials Coordinated by Lyon University Hospital to Assess the Safety and the Efficacy of the IMMUNOtherapy With Domvanalimab + Zimberelimab Combination in Patients With Advanced RARE Cancers

Immune checkpoint inhibitors (ICI) have revolutionized the management of advanced cancers. However, most rare cancers have been excluded from this progress due to the lack of clinical trials involving these diseases. After the standard first-line treatment, there are no other validated treatments for most of them. The management of these patients in ≥ 2nd line treatment relies on historic poorly effective regimens. This creates an inequity between patients with frequent cancers beneficiating from medical progresses and approvals of innovative drugs, and patients with rare cancers are still treated with old and toxic drugs. Few available data on case reports and early phase studies indicate a beneficial role of the immunotherapy in rare cancers. The investigators assume that the combination of Domvanalimab and Zimberelimab is more effective than historical standard treatments in patients with 5 types of advanced rare cancers, after failure of at least one line of standard treatment in the advanced setting: * Cohort 1: Peritoneal Mesotheliomas (PM) * Cohort 2: Gestational Trophoblastic Tumors (GTT) * Cohort 3: B3 Thymomas and Thymic Carcinomas (TET) * Cohort 4: Refractory Thyroid Carcinomas (ATC) * Cohort 5: GEP-NET and carcinoid tumors (GEP-NET (Gastroenteropancreatic neuroendocrine tumors)/TCT (Thoracic carcinoid tumor)/UP-NET (Neuroendocrine tumor of unknown primary)) The primary objective is to assess the efficacy of the combination of Domvanalimab and Zimberelimab in terms of progression-free survival rate at 24 weeks (for cohorts 1,3,5), successful hCG (Human Chorionic Gonadotropin) normalisation rate at 24 weeks for cohort 2 and survival rate for cohort 4. The secondary objectives are to assess the efficacy of the combination of anti-TIGIT (T cell Immunoreceptor with Ig and ITIM domains) and anti-PD-1 (Programmed Death-1) immunotherapies in terms of overall response rate, progression-free survival (cohort 1-3 and 5), resistance-free survival (cohort 2), overall survival (cohorts 1-3 and 5), duration of the response (cohorts 1-3 and 5); and to assess the tolerability of the doublet of immunotherapy in terms of adverse events. Patients will be treated until disease progression or alternatively 2 years in case of complete response (upon discussion with the coordinator of the study, the coordinator of the cohort and the investigator), unacceptable toxicity, or death. At the end of treatment, patients will be followed up for at least 1 year. IMMUNORARE5 is composed of five independent open-label national multicenter single-arm phase II trials, sponsored by Lyon University Hospital, led in collaboration with the corresponding French national reference centers, with a centralized coordination by a dedicated team. Each phase II trial is designed as a two-stage Simon design, with early termination for futility. For each cohort, a null hypothesis (H0) and an alternative hypotheses (H1) regarding the percentages of patients with success has been defined, with 5% one-sided alpha level and 80% power. The trial will be conducted in 15 French Centers with an inclusion period of 36 months