1. Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial
- Author
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Laetitia Dahan, Romain Cohen, Meher Ben Abdelghani, Hélène Castanié, Christophe Tournigand, Jean-Philippe Metges, Paul Gougis, Anthony Turpin, Cindy Neuzillet, Jean-Frédéric Blanc, Dewi Vernerey, David Tougeron, Benoit Rousseau, Marc Hilmi, Marie-Line Garcia-Larnicol, and Alice Boilève
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Durvalumab ,Paclitaxel ,medicine.medical_treatment ,Phases of clinical research ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Adverse effect ,Aged ,Enterocolitis ,Chemotherapy ,Septic shock ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Biliary Tract Neoplasms ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,business ,Tremelimumab ,medicine.drug - Abstract
Background The IMMUNOBIL PRODIGE 57 trial is a non-comparative randomized phase II study assessing the efficacy and safety of the durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) combination with or without weekly paclitaxel in patients with advanced biliary tract carcinoma (BTC) after failure of platinum-based chemotherapy. Taxanes have already been safely combined with immune checkpoint inhibitors in other tumors. We report results of the 20-patient safety run-in. Methods Patients received durvalumab (1500 mg at day 1 [D1] of each cycle)/tremelimumab (75 mg at D1 for 4 cycles; Arm A) or durvalumab/tremelimumab with paclitaxel (80 mg/m2 at D1, D8, D15; Arm B) every 28 days. Results Twenty patients were enrolled (Arm A/B: 10/10). There were no dose-limiting toxicities (DLTs) in Arm A. Six DLTs were observed in five patients (50%) in Arm B, meeting a stopping rule for the trial inclusions. DLTs included three serious anaphylactic reactions (with one cardiac arrest), two enterocolitis, and one infectious pneumopathy with septic shock. There were no patients with history of personal or familial auto-immune disease. Conclusion The safety run-in part of IMMUNOBIL PRODIGE 57 raised concerns regarding co-administration of paclitaxel with durvalumab and tremelimumab in BTC, with an unexpected increase in anaphylactic adverse events. Phase II of the study will only evaluate the durvalumab and tremelimumab combination arm. ClinicalTrials registration NCT03704480 .
- Published
- 2021