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

INTRODUCTION

-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 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) 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 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.