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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

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

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 (NCT06790706) is a Phase 2 interventional studying Peritoneal Mesothelioma and Gestational Trophoblastic Tumor, sponsored by Hospices Civils de Lyon. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Peritoneal Mesothelioma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 154 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Peritoneal Mesothelioma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: General inclusion criteria for all cohorts - 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 - blood count (hemoglobin) at least 9.0 g/dL - Patients with adequate renal function: Calculated kidney function (creatinine clearance) at least 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 willing to sign a consent form prior to participating in any study related procedures. - Patients affiliated to the French social security system or equivalent ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: General inclusion criteria for all cohorts * 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 Specific inclusion criteria for each cohort: * 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. Exclusion Criteria: General exclusion criteria for all cohorts: * Previous treatment with immune checkpoint inhibitors (including anti-TIGIT, anti-PD1, anti-PD-L1, anti-CTLA4), or other types of immunotherapy. * Active or prior documented autoimmune or immune-related disorders (Stevens-Johnson syndrome, immune-related myocarditis, immune-related pneumonitis, immune-related colitis, immune-related hepatitis, immune mediated dermatologic adverse reactions, immune-mediated nephritis). (The following are exceptions to this criterion: Patients with vitiligo or alopecia; Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; Any chronic skin condition that does not require systemic therapy; Patients without active disease and no treatment for the last 5 years may be included but only after consultation with the coordinator of the cohort) * Medical condition that requires chronic systemic steroid therapy, or any other forms of immunosuppressive medication. (For example, patients with autoimmune disease that requires systemic steroids or immunosuppression agents should not to be included. Replacement therapy (eg., thyroxine, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.) * Uncontrolled intercurrent illness, including but not limited to, congestive heart failure; respiratory distress; liver failure; allergy; psychiatric illness/social situations that would limit compliance with study requirement according to the investigator, or that substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. * Patients with a second primary cancer, except for: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other hematological or solid cancers curatively treated with no evidence of disease for ≥ 3 years. * All subjects with meningeal involvement. * Untreated or symptomatic Central nervous system (CNS) metastases. (Patients are eligible if the following criteria are met: * 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. Specific exclusion criteria by cohort: * Cohort 1 (Peritoneal mesothelioma) * Planned cytoreductive surgery or PIPAC within 6 months of study treatment in order to be able to assess the primary endpoint * Cohort 3 (B3 thymomas and thymic carcinomas) * Neuroendocrine tumors * Any mixed histology with A/AB/B2 component * Any paraneoplastic syndrome * Positivity to anti RACh antibodies * Cohort 5 (GEP-NET and carcinoid tumors) * Poorly differentiated neuroendocrine carcinomas * Mixed tumors * Contraindication to FOLFOX-4 (DPD deficiency, i.e. uracilemia levels ≥ 16 ng/mL) * Previous administration of oxaliplatin

Treatments Being Tested

DRUG

DOMVANALIMAB + ZIMBERELIMAB

Patients will be treated with intravenous Domvanalimab at flat dose of 1200 mg + intravenous Zimberelimab at flat dose of 360 mg, administered every 3 weeks (Q3W, one cycle = 3 weeks).

DRUG

DOMVANALIMAB + ZIMBERELIMAB + FOLFOX-4

Patients will be treated with intravenous Domvanalimab at flat doses of 1600 mg + intravenous Zimberelimab at flat dose of 480 mg, administered every 4 weeks (Q4W), together with an induction treatment of intravenous FOLFOX-4 (Oxaliplatin 85 mg/m2 IV, L-folinic acid 200 mg/m2 IV, and fluorouracil 400 mg/m2 IV bolus on Day 1, fluorouracil 2400 mg/m2 IV continuous infusion over 46-48 hours starting on Day 1) given every 2 weeks, for 4 months (one cycle = 4 weeks).

Locations (15)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Institut de Cancerologie de l'Ouest , medical oncology department
Angers, France
Institut Bergonié, medical oncology department
Bordeaux, France
Hospices Civils de Lyon, Thoracic Oncology Department, Louis Pradel Hospital
Bron, France
Centre Hospitalier Universitaire de Lille, medical oncology department
Lille, France
Hospices Civils de Lyon, Medical Oncology Department, Edouard Herriot Hospital
Lyon, France
AP-HM, TIMONE Hospital, medical oncology department
Marseille, France
Institut Paoli-Calmettes Marseille, medical oncology department
Marseille, France
Institut Régional du Cancer de Montpellier, medical oncology department
Montpellier, France
Institut Curie, thoracic oncology department
Paris, France
AP-HP, Tenon Hospital, medical oncology department
Paris, France
Hospices Civils de Lyon, Medical Oncology Department, Lyon SUD Hospital
Pierre-Bénite, France
Centre Eugène Marquis, medical oncology department
Rennes, France
Insitut de Cancérologie Strasbourg Europe, medical oncology department
Strasbourg, France
ONCOPOLE Claudius Regaud, IUCT-Oncopole, medical oncology department
Toulouse, France
Institut Gustave Roussy, medical oncology department
Villejuif, France

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06790706), the sponsor (Hospices Civils de Lyon), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06790706 clinical trial studying?

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 tr… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06790706?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06790706?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06790706. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06790706. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.