86P - Durvalumab plus Olaparib as maintenance therapy in extensive-stage small-cell lung cancer (TRIDENT): updated efficacy and safety analysis

Background

First line durvalumab in extensive-stage small-cell lung cancer (ES-SCLC) demonstrated significant improvement of OS in CASPIAN trial. PARP inhibitors have the potential to confer antitumor activity, modify tumor immunogenicity, and sensitize tumors to anti-PD-1/PD-L1 therapy. Here, we investigated the efficacy and safety of durvalumab plus Olaparib as maintenance therapy in ES-SCLC pts after Durvalumab plus chemotherapy as first line treatment.

Methods

TRIDENT is a single arm, multicenter, phase 2 study. Treatment-naïve 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 at 12 months (APF12). Secondary endpoints included PFS, Overall Survival, Objective Response Rate (according to RECIST1.1.) and safety profile.

Results

60 patients were enrolled from 4 sites in China between August 2021 and August 2022. At the data cutoff on August 9, 2023, the median duration of follow-up was 13.0 months. 10 (16.7%) patients were still receiving study treatment. The primary endpoint of PFS at 12 months was 24.5% (95% CI, 14.3%-36.2%). Median PFS from first line treatment was 6.7 months (95% CI, 5.1-8.4), median overall survival was 14.6 months (95% CI 10.9–21.8); 2 (3.3%) patients received complete response (CR), 42 (70%) patients received partial response (PR) and the ORR was 73.3% (95%CI, 60.3-83.9%). Treatment-emergent adverse events (TEAE) occurred in 58 (96.7%) patients, with 22 (36.7%) of grade ≥3; 15 (25%) patients reported serious adverse events; TEAEs leading to death of any cause occurred in 2 (3.3%) patients.

Conclusions

Durvalumab plus Olaparib as maintenance therapy in ES-SCLC patients showed encouraging anti-tumor activity without new safety signal observed. Further exploration of ES-SCLC subpopulation who may benefit from durvalumab combined with Olaparib modality is needed.

Clinical trial identification

NCT05245994.

Legal entity responsible for the study

Sun Yat-sen University Cancer Center.

Funding

Sun Yat-sen University Cancer Center and AstraZeneca.

Disclosure

All authors have declared no conflicts of interest.