In the present TACTIC clinical trial, the investigators propose to determine the clinical interest and immunological efficacy of a treatment combining MP0317 the FAP (Fibroblast Activation Protein)-dependent CD40 agonist, with anti-PD-L1(Programmed Death-Ligand 1) therapy (durvalumab) and gemcitabine-cisplatin-based chemotherapy in unresectable cholangiocarcinoma.
The main objective is to assess the 12-month progression free survival (PFS) rate in the experimental arm. The trial proposed is a non-comparative proof of concept randomized two-stage phase II. The control arm will serve to verify the good calibration of the null hypothesis made in the experimental arm and to provide "true" controls for translational investigations. A semi-continuous monitoring of toxicity is planned in the experimental arm during the first stage of the study to warrant the tolerability of the experimental treatment and then to guarantee the security of the patients.
75 patients (50 in the experimental arm) will be included. The investigators will also decipher, as a translational objective, the molecular and immunological parameters determining the clinical outcomes.
Signed and dated informed consent
Histologically confirmed biliary tract carcinoma: intra/extrahepatic cholangiocarcinoma (note that gallbladder carcinoma are not eligible)
Locally advanced unresectable or metastatic
Patient who had not previously received systemic anti-cancer treatment (adjuvant treatment with Capecitabine is allowed if the end of the chemotherapy was at least 6 months ago)
Patients previously exposed to anti-tumor immunotherapy such as anti-PD-1, anti-PD-L1, or anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) agent or any immune therapy
Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer
Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
Current participation in a study of an investigational agent or in the period of exclusion
Parallel
MP0317 + Gemcitabine + Cisplatine + Durvalumab
Drug* MP0317: 3 mg/kg IV(intraveinous), day 1, every 3 weeks for a maximum of 5 administrations * Immuno-chemotherapy (ICT): cycle 1-5 * Durvalumab 1500 mg IV, day 8 every 3 weeks * Gemcitabine 1000 mg/m² IV, days 8 and 15 every 3 weeks * Cisplatin 25 mg/m² IV, days 8 and 15 every 3 weeks * Immuno-chemotherapy (ICT): cycle 6-8 * Durvalumab 1500 mg IV every 3 weeks * Gemcitabine 1000 mg/m² at day 1, 8 every 21 days * Cisplatin 25 mg/m² at day 1, 8 every 21 days * Then durvalumab (1500 mg IV) will be administrated in monotherapy maintenance every 4 weeks until progression or unacceptable toxicity.
CT-Scan
Procedure/Surgeryat baseline, every 6 weeks (± 1 week) for the first 24 weeks and then every 8 weeks until progression, at end of treatment visit, At each follow-up visit : Only for patients who have not progressed during treatment phase
Gemcitabine + Cisplatin + Durvalumab
Drug* Immuno-chemotherapy (ICT) for 8 cycles : * Durvalumab 1500 mg IV, day 1 every 3 weeks * Gemcitabine 1000 mg/m² IV, days 1 and 8 every 3 weeks * Cisplatin 25 mg/m² IV, days 1 and 8 every 3 weeks * Then durvalumab (1500 mg IV) will be administrated in monotherapy maintenance every 4 weeks until progression or unacceptable toxicity.
progression free survival status (PFS) at 12 months
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Centre Hospitalier Universitaire de Besancon
Lead sponsor
Molecular Partners AG
Collaborator
