Activity of the Hsp90 inhibitor Luminespib Among Non-Small Cell Lung Cancers Harboring EGFR Exon 20 Insertions.

Background: There are currently no approved targeted therapies for NSCLC patients with EGFR exon 20 insertions (ins20), a subgroup of EGFR mutations which are generally refractory to 1st/2nd generation EGFR inhibitors. We report the final results of a phase II trial evaluating the activity of the Hsp90 inhibitor luminespib (AUY922) in NSCLC patients with EGFR ins20.

Patients and Methods: 29 patients with stage IV NSCLC with EGFR ins20 identified on local testing and at least one prior therapy were enrolled on the trial between 8/2013 and 10/2016. The primary endpoint was objective response rate (ORR), with a pre-determined target rate of effectiveness (defined as the rate of partial response (PR) plus stable disease (SD) lasting ≥ 3 months) of 20%. Secondary endpoints were PFS, OS, safety and response by EGFR ins20 subtype.

Results: Among the 29 patients (18 female, median age 60 years,) the ORR was 17%, median progression-free survival (mPFS) was 2.9 mos (95% CI, 1.4-5.6,) and mOS was 13 mos (95% CI, 4.9-19.5.) The results exceeded the pre-determined target rate of effectiveness with 11/29 (38%) patients having a PR or SD ≥ 3 months. The most common luminespib-related toxicities were diarrhea (83%,) visual changes (76%) and fatigue (45%). All study treatment was stopped on 2/28/17 due to dissolution of study drug availability; 3 patients were on treatment at study termination.

Conclusion: The study met its primary endpoint, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted.