Tremelimumab in combination with durvalumab in first or second-line mesothelioma patients: Safety analysis from the phase II NIBIT-MESO-1 study.
8558 Background: The anti-CTLA-4 tremelimumab at two different dose-schedules of administration showed promising activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015). These initial results and the efficacy of targeting the PD-1/PD-L1 axis in different tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the efficacy and safety of tremelimumab combined with the anti-PD-L1 durvalumab in mm patients. We report the safety analysis from the fully-enrolled NIBIT-MESO-1 study. Methods: The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty mm patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are safey, ir-disease control rate, ir-progression free survival, and overall survival. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0. (ClinicalTrials.gov Id: NCT02588131). Results: From October 2015 to October 2016, 40 mm patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. mm histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of January 2017, 12 first or 28 second-line mm patients received a median of 5.5 doses of therapy (range = 1-13). Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity). Conclusions: The combination of tremelimumab and durvalumab is safe and manageable in mm patients. Clinical trial information: NCT02588131.