Durvalumab in ≥ 3rd-line EGFR mutant/ALK+, locally advanced or metastatic NSCLC: Results from the phase 2 ATLANTIC study

Abstract

Background: Anti-PD-1/PD-L1 therapies have demonstrated meaningful clinical benefit in pts with EGFR/ALK wild-type (WT) advanced NSCLC. However, to our knowledge these agents have never been investigated in a study prospectively focusing on NSCLC pts with EGFR mutations or ALK alterations (EGFRmut/ALK+), a distinct subgroup with clear biological and treatment outcome differences compared with EGFR/ALKWTpts. Durvalumab is an engineered human IgG1 mAb targeting PD-L1. Methods: ATLANTIC (NCT02087423) was a Phase 2, open-label, single-arm trial in pts with locally advanced or metastatic Stage IIIB-IV NSCLC (WHO PS 0 or 1;2 prior systemic regimens, including 1 platinum-based and 1 TKI [EGFRmut/ALK+ pts]). There was no maximum number of prior treatments. The study initially enrolled all-comers and then was restricted to pts with PD-L1 high tumours (25% of tumour cells with membrane staining). The study included 3 pt cohorts defined by EGFR/ALK status and tumor PD-L1 expression; here we report results from EGFRmut/ALK+ pts (Cohort 1). The primary outcome was ORR (RECIST v1.1). Secondary outcomes included DCR, DoR, PFS, OS, and safety (CTCAE v4.03). Results: As of 3 June 2016, 111 pts (median age 61 years, 63% female, 59%WHOPS 1 99% non-squamous histology; 59% never smokers; mean prior therapies 3.8) had received durvalumab (10 mg/kg i.v. q2w for 12 months). Responses were durable. Most AEs were low grade. Immune-mediated AEs were manageable with standard treatment guidelines; 5.4%of pts had Grade 3 treatment-related (TR) AEs and 0.9% had TRAEs leading to discontinuation. (Table presented) Conclusions: Although the ORR was somewhat lower compared with that reported in Cohort 2 (EGFR/ALK WT), durable responses were still observed in this heavily pretreated metastatic EGFRmut/ALK+ NSCLC population. However, the data were limited by the short duration of follow up and further confirmation is needed. Activity was greater for pts with high PD-L1 expression. The tolerability profile was manageable.