Phase II study of durvalumab plus olaparib as maintenance therapy in extensive-stage small-cell lung cancer (TRIDENT): Preliminary efficacy and safety results.

Abstract

8518 Background: First-line durvalumab in extensive-stage small-cell lung cancer (ES-SCLC) demonstrated significant improvement of OS in phase Ⅲ CASPIAN trial. PARP inhibitors have the potential to confer antitumor activity, modify tumor immunogenicity, and sensitize tumors to anti-PD-1/PD-L1 therapy. Durvalumab in combination with Olaparib (a PARPi) had clinical activity in relapsed SCLC in a phase Ⅰ/Ⅱ study. This phase Ⅱ study aimed to assess the efficacy and safety of durvalumab plus olaparib as maintenance therapy in patients with ES-SCLC. Methods: TRIDENT is a single arm, multicenter, phase Ⅱ study. Treatment-naive ES-SCLC aged ≥18 with ECOG PS 0-2 were eligible. Durvalumab (1500 mg) was concurrently administered with platinum–etoposide every 3 weeks for 4 cycles, followed by durvalumab 1500 mg every 4 weeks plus olaparib 300 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was the rate of progression free survival (PFS) at 12 months, the secondary endpoints included progression free survival, objective response rate (ORR) according to RECIST 1.1, duration of response (DoR), overall survival (OS) and safety profile. All patients should provide tumor sample for biomarker analysis (exploratory endpoint). Results: Between August 2021 and August 2022, 60 eligible patients were enrolled from 4 sites in China. At data cut-off (Jan 16th, 2023), 18 (30%) patients were still on treatment. The median age was 63 years (range 57-68). The median cycle of durvalumab was 7 (range 1-17), and durvalumab plus olaparib as maintenance therapy was 3.5 (range 1-13). The PFS rate at 6-, 9-, 12-month were 49.7% [95%CI 37.8%-65.4%], 26.3% [95%CI 13.8%-40.3%] and 18% [95%CI 9.3%-34.7%], respectively. ORR was 75% (45/60), the median DoR was 5.0 months [95%CI 3.8-6.5]. With a median follow-up of 10.5 months, the median PFS was 5.8 months [95%CI 4.9-7.7] as calculated from the first cycle of durvalumab plus chemotherapy. The median OS was not reached [95%CI 10-NA]. Of all, treatment emergent adverse event (AE) occurred in 93.3% (56/60) patients, and AEs ≥ grade 3 occurred in 36.7% (22/60) patients. There were no unexpected adverse events identified in this study. There were 5 patients (8.3%) discontinued treatment and 1 death (1.6%) due to AE. Biomarker analysis is still on-going and will be presented in the meeting. Conclusions: TRIDENT is the first study to evaluate the efficacy and safety of durvalumab plus olaparib as maintenance therapy in Chinese ES-SCLC patients to date. The preliminary result warrant further investigation of this treatment modality in ES-SCLC. Clinical trial information: NCT05245994 .