JTO Clinical and Research Reports (Feb 2025)

Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation–Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE)

  • Chee Khoon Lee, PhD,
  • Bin-Chi Liao, MD,
  • Shalini Subramaniam, MMed (Clin Epi),
  • Chao-Hua Chiu, MD,
  • Antony J. Mersiades, MMed (Clin Epi),
  • Chao-Chi Ho, MD, PhD,
  • Chris Brown, MBiostats,
  • Chun-Liang Lai, MD, PhD,
  • Brett G.M. Hughes, M.B.B.S. (Hons),
  • Tsung-Ying Yang, MD, PhD,
  • Ken O’Byrne, MD,
  • Yung-Hung Luo, MD, PhD,
  • Sonia Yip, PhD,
  • Ching-Liang Ho, MD,
  • Victoria Bray, PhD,
  • Wu-Chou Su, MD, PhD,
  • Melissa Moore, PhD,
  • Wei-Lien Feng, MS,
  • Ya-Ying Bai, MS,
  • Kate Ford, MHSc,
  • Michelle M. Cummins, PhD,
  • Martin R. Stockler, MSc (Clin Epi),
  • Benjamin J. Solomon, PhD,
  • Thomas John, PhD,
  • James Chih-Hsin Yang, MD, PhD

Journal volume & issue
Vol. 6, no. 2
p. 100771

Abstract

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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.

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