Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation-Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE)
- Author(s)
- Lee, CK; Liao, BC; Subramaniam, S; Chiu, CH; Mersiades, AJ; Ho, CC; Brown, C; Lai, CL; Hughes, BGM; Yang, TY; O'Byrne, K; Luo, YH; Yip, S; Ho, CL; Bray, V; Su, WC; Moore, M; Feng, WL; Bai, YY; Ford, K; Cummins, MM; Stockler, MR; Solomon, BJ; John, T; Chih-Hsin Yang, J;
- Details
- Publication Year 2025-02,Volume 6,Issue #2,Page 100771
- Journal Title
- JTO Clinical and Research Reports
- Publication Type
- Research article
- Abstract
- INTRODUCTION: EGFR-mutant NSCLC is associated with low mutation burden and low levels of PD-L1 expression. We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in EGFR-mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs). METHODS: Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. Participants were divided into two cohorts: (1) EGFR exon 20 T790M negative (T790M-, progressing on either first-line osimertinib, or on a single line of first/second generation TKI), and (2) T790M positive (T790M+, progressing on greater than or equal to 1 lines of TKI, including osimertinib). The primary endpoint was the confirmed objective response rate (ORR) assessed by the investigators. Progression-free survival and safety were secondary outcomes. RESULTS: One hundred participants from Australia and Taiwan were enrolled. Median follow-up was 26 months with 88% and 96% experiencing progression events for T790M- and T790M+, respectively. The ORR for T790M- was 31% (95% confidence interval: 20-45), including two complete responses. The ORR for T790M+ was 21% (95% confidence interval: 12-34). Median durations of response were 9.5 months and 6.3 months for T790M- and T790M+, respectively; median progression-free survival rates were 6.5 months and 4.9 months, respectively. For T790M-, ORR was 27% for 50% or higher PD-L1 (n = 22) and 0% for less than 50% PD-L1 (n = 10), respectively. For T790M+, ORR was 17% for 50% or higher PD-L1 (n = 24). The safety profile was consistent with previous reports. CONCLUSIONS: Durvalumab, tremelimumab, and platinum-pemetrexed had modest anti-tumor activity in EGFR-mutant NSCLC after progression on TKI. The T790M- cohort had higher ORR and a longer duration of response. Immune adverse events were not increased with tremelimumab. The clinical registration number of this trial is NCT03994393.
- Publisher
- Elsevier
- Keywords
- Checkpoint inhibitors; Chemotherapy; EGFR mutation; Non-small cell lung cancer
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.jtocrr.2024.100771
- Open Access at Publisher's Site
https://doi.org/10.1016/j.jtocrr.2024.100771- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-30 02:31:29
Last Modified: 2025-01-30 02:34:12