A multi-institutional, single-arm, phase 2 study of durvalumab plus amrubicin in patients with relapsed extensive-stage small cell lung cancer (Aphrodite trial).

Abstract

8105 Background: In patients (pts) with sensitive relapsed (SR) and refractory relapsed (RR) small cell lung cancer (SCLC), amrubicin (AMR) is one of the current standard treatments in Japan. However, the overall survival (OS) in RR is particularly poor, with approximately 6-9 months and a 1-year overall survival rate (1yr-OS rate) of 34%, which is not satisfactory. We conducted the phase 2 exploratory proof-of-concept trial based on preclinical results, which showed that the combination of an anti-PD-1 antibody and a topoisomerase II inhibitor had a synergistic effect on cancer cells. This trial was funded by AstraZeneca K.K. Methods: This trial enrolled pts with SR or RR SCLC that recurred after first-line chemo-immunotherapy. They were treated with durvalumab (1,500 mg on day1) and AMR (40 mg/m 2 on days1-3), every three weeks until progression. After assessing the safety of the combination therapy in the lead-in cohort, we initiated the phase 2 part of the trial. The primary endpoint was the 1yr-OS rate calculated based on a year consisting of 48 weeks. The secondary endpoints consisted of OS, progression-free survival (PFS), overall response rate (ORR) etc. The expected 1yr-OS rate for SR and RR were 61.1% and 44.4%, respectively, which were 10% higher than the systematic review result for AMR alone in Japanese pts. Based on this review result and considering feasibility, the sample size was planned as 18 pts for each SR and RR. Results: Between July 2022 and August 2024, a total of 23 (SR: 5; RR: 18) pts were enrolled. All pts had previously received treatment with platinum-containing drugs and immune checkpoint inhibitors (ICI). The SR group could not be enrolled till sufficient sample size for statistical analysis. The 1yr-OS rate was 80.0% for SR group, which included a complete responder. The efficacy results for the RR group were: The 1yr-OS rate was 44.4% (95% confidence interval (CI): 21.6-65.1). The median PFS and OS were 15.1 weeks (95% CI: 11.0-23.3) and 43.1 weeks (95% CI: 24.6-64.3), respectively. The ORR was 38.9% (95% CI: 17.3-64.3). Grade 3 or higher adverse events were observed in 65.2% of all 23 pts, but no new events beyond those previously reported were identified. The most frequent Grade 3 or higher adverse event was neutropenia (43.5%), with febrile neutropenia occurring in 13.0%. Grade 3 or higher pneumonia was observed in 4.3%, and no treatment-related deaths were reported. Conclusions: The combination therapy of durvalumab and AMR suggests favorable efficacy and tolerable safety, particularly in pts with RR, even in those who had already received ICI treatment. Clinical trial information: jRCT2061220036.