Pembrolizumab Plus Amrubicin in Patients With Relapsed SCLC: Multi-Institutional, Single-Arm Phase 2 Study

INTRODUCTION: In patients with relapsed SCLC, amrubicin (AMR) is the current standard treatment in Japan. Nevertheless, its efficacy is not satisfactory and prognosis is poor. Preclinical study suggested that anthracycline agent might induce immunogenic cell death and work synergistically with immune checkpoint inhibitors. METHODS: Patients with relapsed SCLC who relapsed after completion of platinum-containing regimen were registered. Patients were treated with pembrolizumab (200 mg, flat dose on d 1, every 3 wk for 2 y) plus AMR (40 mg/m(2) on d 1–3, every 3 wk until progression). Primary end point was overall response rate (ORR). Secondary end points consisted of progression-free survival (PFS), overall survival, and safety. On the basis of the hypothesis that this treatment will improve ORR from 20% to 40% (0.1 of one-sided α and power of 0.8), 25 patients are required (trial identifier: NCT03253068). RESULTS: Between November 2017 and October 2019, a total of 25 patients were enrolled. Most participants (88%) relapsed within 90 days after platinum-containing therapy and all patients were immune checkpoint inhibitor-naive. ORR, the primary end point, was 52.0% (95% confidence interval [CI]: 31.3%–72.2%). Median PFS was 4.0 months (95% CI: 2.8–7.0 mo), and PFS rate at 1 year was 14.4%. Median overall survival was 10.6 months (95% CI: 7.3–21.3 mo). Common adverse events greater than or equal to grade 3 were neutropenia (64%), leukopenia (40%), and febrile neutropenia (16%). No treatment-related deaths occurred. CONCLUSIONS: Among patients with relapsed SCLC, pembrolizumab plus AMR was effective and tolerable.