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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
EU CTIS ID: 2024-517254-99-00
What this study is testing
The primary objective is to assess the efficacy of the combination of Domvanalimab and Zimberelimab in patients with 5 types of advanced rare cancers (peritoneal mesotheliomas, gestational trophoblastic tumors, thymic carcinomas, anaplastic thyroid carcinomas, and GEP-NET & carcinoid tumors) in progression/resistance after at least one standard line of treatment.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Histologically proven advanced solid tumors that progressed/resisted after minimum one line of standard systemic treatment, or resisted during the first-line of treatment
- Specific inclusion criteria for Cohort 2 : Evidence of resistance or relapse after at least one line of polychemotherapy (e.g. EP low dose, BEP regimen, EMA-CO regimen …)
- Specific inclusion criteria for Cohort 3 : Thymic carcinoma, histologically confirmed by a referent pathologist of the RYTHMIC network
- 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)
- Specific inclusion criteria for Cohort 3 : Evidence of progression or relapse after at least one line of platinum-based chemotherapy
- Specific inclusion criteria for Cohort 4 : Anaplastic thyroid carcinoma with non-mutated or mutated B-RAF, histologically or cytologically-confirmed by a referent pathologist of the Tuthyref network
You likely can't join if
- Previous treatment with immune checkpoint inhibitors (including anti-TIGIT, anti-PD1, anti-PD-L1, anti-CTLA4,), or other types of immunotherapy
- Time window of less than 4 weeks between the last cycle of systemic treatments or the last day of radiotherapy and the first dose of study treatment (or less than 5 half-lives of the previous agents, if shorter than 4 weeks). An exception applies for palliative radiotherapy administered locally to control local symptoms likely to compromise the patient functional status (e.g., pain, compression, hemorrhage), as such treatment is not expected to interfere with the assessment of the efficacy or safety of the investigational systemic therapy given concurrently. For patients with rapidly progressive malignancies that may fast compromise their vital status, a minimum interval of two weeks between the last cycle of platinum-based chemotherapy (with or without concurrent radiotherapy) or the last day of radiotherapy, and the start of study treatment, is acceptable, upon approval by one of the two coordinators of the cohort. Patients receiving bisphosphonates for bone metastases may remain on a stable dose regimen, provided that treatment was initiated at least 4 weeks before the first administration of the 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.
- Specific exclusion criteria for Cohort 5 : Poorly differentiated neuroendocrine carcinomas
- Specific exclusion criteria for Cohort 5 : Mixed tumors
See the full eligibility criteria
Who can join
- Histologically proven advanced solid tumors that progressed/resisted after minimum one line of standard systemic treatment, or resisted during the first-line of treatment
- Specific inclusion criteria for Cohort 2 : Evidence of resistance or relapse after at least one line of polychemotherapy (e.g. EP low dose, BEP regimen, EMA-CO regimen …)
- Specific inclusion criteria for Cohort 3 : Thymic carcinoma, histologically confirmed by a referent pathologist of the RYTHMIC network
- 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)
- Specific inclusion criteria for Cohort 3 : Evidence of progression or relapse after at least one line of platinum-based chemotherapy
- Specific inclusion criteria for Cohort 4 : Anaplastic thyroid carcinoma with non-mutated or mutated B-RAF, histologically or cytologically-confirmed by a referent pathologist of the Tuthyref network
- Specific inclusion criteria for Cohort 4 : 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
- Specific inclusion criteria for Cohort 4 : In B-RAF mutated anaplastic thyroid carcinoma: evidence of progression after a standard B-RAF inhibitor
- Specific inclusion criteria for Cohort 5 : 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
- Specific inclusion criteria for Cohort 5 : Indication of oxaliplatin-based regimen treatment
- Specific inclusion criteria for Cohort 5 :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.
- Life expectancy ≥ 16 weeks
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort A = Patients who gave their informed consent to participate to the IMMUNORARE5 clinical trial
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort A = Patients with gestational trophoblastic tumors (including placenta site trophoblastic tumors and epithelioid carcinomas), histologically-confirmed by a referent pathologist the French National Center for Trophoblastic Diseases
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort A = Patients who are eligible to participate to the IMMUNORARE5 trial and to receive domvanalimab and Zimberelimab treatments (i.e. patients who successfully completed the screening procedures)
- 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)
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort A = Signed informed consent prior to participating in this study related procedures.
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort B = Male partner of a patient enrolled in the IMMUNORARE5 trial who meets the inclusions criteria for cohort A
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort B = Male partner who fathered the pregnancy that gave rise to the gestational trophoblastic tumor
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort B = Subjects older than 18 years
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort B = Signed informed consent prior to participating in this study related procedures.
- Specific inclusion criteria for Exploratory study TROPHOGEN : Cohort B = Subjects affiliated to the French social security system or beneficiaries of a similar scheme
- Highly effective contraception for men and childbearing age women. Effective contraceptive methods and guidelines can be found in the Annex 1 of this protocol (Breastfeeding is prohibited during the participation in IMMUNORARE trial)
- 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 coordinator of the cohort)
- Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment: •Absolute Neutrophil count > 1.5x 10^9/L; •Platelets count ≥ 100 X 10^9/L; •Hemoglobin ≥ 9 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 (≤ 3 x ULN for patients with known Gilbert’s syndrome), AST/ALT ≤ 2.5 X UNL (≤ 5 X UNL for patients with liver metastases)
- Participation in IMMUNORARE5 trial testing DOMVANALIMAB and ZIMBERELIMAB, validated by a multidisciplinary tumor board recognized by the national reference center, , or validated by at least one national coordinator of the cohort
- Signed informed consent prior to participating in any study related procedures.
- Patients affiliated to the French social security system
- Patient able to comply with the protocol, including follow-up visits and examinations
- Specific inclusion criteria for Cohort 1 : Histologically-confirmed malignant peritoneal mesotheliomas (epithelioid, sarcomatoid, or biphasic)
- Specific inclusion criteria for Cohort 1 : Evidence of progression or recurrence after at least one line of platinum based-chemotherapy regimen (Previous treatment with pressurized intra-peritoneal aerosol chemotherapy (PIPAC) is authorized)
- Specific inclusion criteria for Cohort 2 : 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)
What rules you out
- Previous treatment with immune checkpoint inhibitors (including anti-TIGIT, anti-PD1, anti-PD-L1, anti-CTLA4,), or other types of immunotherapy
- Time window of less than 4 weeks between the last cycle of systemic treatments or the last day of radiotherapy and the first dose of study treatment (or less than 5 half-lives of the previous agents, if shorter than 4 weeks). An exception applies for palliative radiotherapy administered locally to control local symptoms likely to compromise the patient functional status (e.g., pain, compression, hemorrhage), as such treatment is not expected to interfere with the assessment of the efficacy or safety of the investigational systemic therapy given concurrently. For patients with rapidly progressive malignancies that may fast compromise their vital status, a minimum interval of two weeks between the last cycle of platinum-based chemotherapy (with or without concurrent radiotherapy) or the last day of radiotherapy, and the start of study treatment, is acceptable, upon approval by one of the two coordinators of the cohort. Patients receiving bisphosphonates for bone metastases may remain on a stable dose regimen, provided that treatment was initiated at least 4 weeks before the first administration of the 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.
- Specific exclusion criteria for Cohort 5 : Poorly differentiated neuroendocrine carcinomas
- Specific exclusion criteria for Cohort 5 : Mixed tumors
- Specific exclusion criteria for Cohort 5 : Contra-indication to FOLFOX-4 (DPD deficiency, i.e. uracilemia levels ≥ 16 ng/mL)
- 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 for Cohort 3 : Any paraneoplastic syndrome
- Specific exclusion criteria for Cohort 1 : Planned cytoreductive surgery or PIPAC within 6 months of study treatment in order to be able to assess the primary endpoint
- Specific exclusion criteria for Cohort 3 : Neuroendocrine tumors
- Specific exclusion criteria for Cohort 3 : Any mixed histology with A/AB/B2/B3 component
- Specific exclusion criteria for Cohort 5 : Previous administration of oxaliplatin
- Specific exclusion criteria for Exploratory study TROPHOGEN : Cohort A = Absence of archival tumor tissue and impossibility to obtain a new biopsy
- Specific exclusion criteria for Exploratory study TROPHOGEN : Cohort A = Impossibility to realize a blood drawn
- Specific exclusion criteria for Exploratory study TROPHOGEN : Cohort B = Persons under tutorship or guardianship
- Specific exclusion criteria for Exploratory study TROPHOGEN : Cohort B = Persons deprived of their liberty by a judicial or administrative decision
- Specific exclusion criteria for Exploratory study TROPHOGEN : Cohort B = Persons under psychiatric care
- Specific exclusion criteria for Exploratory study TROPHOGEN : Cohort B = Impossibility to realize a blood drawn
- Specific exclusion criteria for Cohort 3 : Positivity to anti RACh antibodies
- Active or prior documented autoimmune disorders. (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 coordinator of the cohort)
- Medical condition that requires chronic systemic steroid therapy with prednisone > 10 mg daily (or equivalent), 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
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.