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

Inclusion Criteria

• •Histologically proven advanced solid tumors that progressed/resisted after minimum one line of standard systemic treatment, or resisted during the first-line of treatment
• •No indication of curative surgery for this disease at inclusion (For cohort 1 only (peritoneal mesothelioma), debulking surgery could be considered after minimum 6 months of study treatment in the case of important tumor response)
• •Evaluable lesions (target or non-target lesions) for radiological response according to RECIST 1.1 (cohorts 3, 4, 5), or mRECIST (cohort 1), or assessable for biological response with serum hCG (cohort 2)
• •Patients older than 18 years
• •Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• •Patients must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy in absence of medical contraindication (If either a fresh biopsy or archival material is not available, patient inclusion has to be discussed and validated with the coordinators of the cohort)
• •Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment:
• •* Absolute Neutrophil count \> 1.5 x 109/L
• •* Platelets count ≥ 100 X 109/L
• •* Hemoglobin ≥ 9.0 g/dL
• •Patients with adequate renal function: Calculated creatinine clearance ≥ 30 ml/min according to the local institutional standard method (MDRD preferred)
• •Serum bilirubin ≤ 1.5 x UNL (Upper Normal Limit) (\< 3 x UNL for patients with known Gilbert's syndrome), AST/ALT ≤ 2.5 X UNL (≤ 5 X UNL for patients with liver metastases)
• •Life expectancy ≥ 16 weeks
• •Highly effective contraception for men and childbearing age women.
• •Signed informed consent prior to participating in any study related procedures.
• •Patients affiliated to the French social security system or equivalent
• •Patient able to comply with the protocol, including follow-up visits and examinations
• •Cohort 1 (Peritoneal mesothelioma)
• •* Histologically-confirmed malignant peritoneal mesotheliomas (epithelioid, sarcomatoid, or biphasic)
• •* Evidence of progression or recurrence after at least one line of platinum + pemetrexed based-chemotherapy regimen (Previous treatment with pressurized intra-peritoneal aerosol chemotherapy (PIPAC) is authorized)
• •Cohort 2 (Gestational trophoblastic tumors)
• •* Gestational trophoblastic tumors (including placenta site trophoblastic tumors and epithelioid carcinomas) histologically or cytologically-confirmed by a referent pathologist of the French National Center for Gestational Trophoblastic Diseases (In exceptional cases, the patients with typical clinical presentation of gestational trophoblastic tumors with elevated hCG, and experiencing resistance to polychemotherapy, can be included even if the gestational trophoblastic tumor was not histologically or cytologically-confirmed, provided that the French gestational trophoblastic center has validated the case and the inclusion of the patient)
• •* Evidence of resistance or relapse after at least one line of polychemotherapy (e.g. EP low dose, BEP regimen, EMA-CO regimen …)
• •Cohort 3 (B3 thymomas and thymic carcinomas)
• •* B3 thymomas and thymic carcinoma, histologically confirmed by a referent pathologist of the RYTHMIC network
• •* Evidence of progression or relapse after at least one line of platinum-based chemotherapy
• •Cohort 4 (Anaplastic thyroid carcinomas)
• •* Anaplastic thyroid carcinoma with non-mutated or mutated B-RAF, histologically or cytologically-confirmed by a referent pathologist of the Tuthyref network
• •* In B-RAF non-mutated anaplastic thyroid carcinomas: Persistent disease at the first evaluation after chemoradiation or disease progression/relapse after the end of chemoradiation
• •* In B-RAF mutated anaplastic thyroid carcinoma: evidence of progression after a standard B-RAF inhibitor
• •Cohort 5 (GEP-NET and carcinoid tumors)
• •* Histologically or cytologically-confirmed well-differentiated neuroendocrine tumor (WHO classification as NET G1, G2 or G3), or typical/atypical carcinoid tumor (according to WHO classification for thoracic NETs), from gastroenteropancreatic, thoracic (thymus or lung) or unknown primary origin
• •* Indication of oxaliplatin-based regimen treatment
• •* Evidence of progression or relapse after at least 1 line of systemic treatment, such as somatostatine analog, or targeted agents such as everolimus or sunitinib, or chemotherapy without oxaliplatin, or peptide receptor radionuclide therapy.
• •* CNS lesions are asymptomatic and previously treated.
• •* Patient does not require ongoing steroid treatment
• •* Imaging demonstrates stability of disease 28 days from last treatment for CNS metastases.)
• •Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 6 weeks from the last dose prior to study treatment (or at least 5 half-lives depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
• •Treatment with other investigational agents prone to interact with outcomes of the trial upon to investigator opinion.
• •Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorders that do not allow oral medication such as malabsorption.
• •Active HIV, HBV or HCV infection.
• •Prior organ transplantation, including allogeneic stem cell transplantation (excluding autologous bone marrow transplant).
• •Ongoing participation in any other clinical trial who may interfere with the present study in the judgment of the investigator
• •Patients under tutorship or guardianship.