Feasibility study of nivolumab and docetaxel in previously treated patients with advanced non-small cell lung cancer

Abstract

Objective: Nivolumab (NIV) is a standard second-line treatment for previously treated patients with advanced non-small cell lung cancer (NSCLC). Although greater efficacy might be expected from a combination of NIV and a cytotoxic agent for advanced NSCLC, verification in a clinical trial is required. Since few reports on NIV+docetaxel (DTX) combination therapy are available, we performed a feasibility study that examined the safety of this combination therapy prior to large-scale clinical trials. Methods: Eligibility criteria included a history of platinum-based chemotherapy, PS 0-1, and adequate organ function. Patients received NIV 3 mg/kg (days 1 and 15) and DTX 60mg/m2 (day 1) every 4 weeks for a maximum of 2 courses. The primary endpoints were safety of and dose-limiting toxicity (DLT) in the first course. This study used a 3 +3 design and was considered to be feasible if DLT occurred in one-third or less of the patients. The secondary endpoints were adverse events and a response rate. The DLT was defined in accordance with the phase Ib study by Kanda et al (Ann Oncol 2016). Results: Between Aug 2016 and Sep 2016, three patients were enrolled in this trial at 2 centers in Japan. The first, second, and third study participants were: a 57-year-old woman with adenocarcinoma, a 44-year-old man with squamous cell carcinoma, a 58-year-old man with adenocarcinoma. Grade 3 or more adverse events occurred in only 1 patient(grade 4 neutropenia), and no DLT was observed in any patient. All patients completed 2 courses, with objective tumor responses of PD, SD and PR. Conclusion: NIV+ DTX combination therapy was safe, and further evaluation is warranted. Since combination NIV plus cytotoxic therapy has not been approved, we (Thoracic Oncology Research Group [TORG]) are planning a phase II/III trial that compares NIV+ DTX with NIV alone for previously treated patients with advanced NSCLC, using an Advanced Medical Healthcare in Japan.