Durvalumab, tremelimumab and platinum chemotherapy in EGFR mutation positive non-small cell lung cancer - an open label phase 2 trial (ILLUMINATE)

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 following progression with EGFR tyrosine kinase inhibitors (TKIs). Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. Participants were divided into two cohorts: (1) T790M- (EGFR exon 20 T790M negative, progressing on either first-line osimertinib, or on a single line of first/second generation TKI), or (2) T790M+ (T790M positive, progressing on ≥1 lines of TKI, including osimertinib). The primary endpoint was confirmed objective response rate (ORR) assessed by investigators. Progression-free survival (PFS) and safety were secondary outcomes. One hundred participants were enrolled from Australia and Taiwan. Median follow-up was 26 months with 88% and 96% experiencing progression events for T790M- and T790M+, respectively. ORR for T790M- was 31% (95% CI 20-45), including 2 complete responses. ORR for T790M+ was 21% (95% CI 12-34). Median durations of response (DoR) were 9.5 months and 6.3 months for T790M- and T790M+, respectively; median PFS were 6.5 months and 4.9 months, respectively. For T790M-, ORR was 27% for PD-L1≥50% (N=22) and 0% for PD-L1