Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study

Introduction: Thymic carcinoma (TC) is a rare cancer with a poor prognosis and limited treatment options, especially after relapse. Methods: In this open-label, two-stage, multicentre, single-arm and phase II trial, the main eligibility criteria were unresectable or recurrent TC, an Eastern Cooperative Oncology Groupeperformance status of 0 or 1, progression after at least one chemo(radio) therapy and no history of autoimmune disease. Nivolumab was administered at a dose of 3 mg/kg every 2 weeks. The primary end-point was response rate (RR) as evaluated by central review using Response Evaluation Criteria In Solid Tumours (RECIST), version 1.1. The planned sample size was 15 for each stage, with a threshold RR of 5%, an expected RR of 20%, one-sided alpha of 5% and power of 80%. Results: Between July 1 and August 16 2016, 15 patients were accrued in the first stage. Response was assessable in all patients, and 13 had squamous histology. Median follow-up time was 14.1 months (range: 2.4-17.5). The median number of nivolumab received was eight (range: 3-33). RR was 0% (95% confidential interval [CI]: 0-21.8). Eleven patients had stable disease (SD) including five patients with SD for 24 or more weeks. Median progression-free survival was 3.8 months (95% CI: 1.9-7.0). Two patients experienced immune-related serious adverse events (grade III aspartate aminotransferase (AST) increase and grade II adrenal insufficiency). Because the early termination criteria (less than one responder) were fulfilled during the first stage, the patient accrual was terminated. Conclusions: Despite the small number of patients, nivolumab was unable to produce tumour shrinkage by RECIST in previously treated unresectable or recurrent TC. (C) 2019 The Authors. Published by Elsevier Ltd.