Efficacy and safety of lorlatinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) previously treated with 2nd-generation ALK TKIs

Abstract

Background: Standard therapy for advanced anaplastic lymphoma kinase (ALK)+ NSCLC consists of first-line crizotinib, followed by 2nd-generation ALK tyrosine kinase inhibitors (TKIs) such as ceritinib, alectinib, or brigatinib. While pts can achieve some clinical benefit from these agents, most will subsequently develop resistance. Lorlatinib, a brain-penetrant next-generation ALK TKI, is active against most known resistance mutations that can develop during treatment with 1st- and 2nd-generation TKIs. Here, we explore the antitumor activity and safety of lorlatinib in pts with ALK+ NSCLC treated with ≥1 prior 2nd-generation TKI. Methods: In this ongoing phase 2 study (NCT01970865), pts with ALK+ or ROS1+ NSCLC,6asymptomatic untreated or treated central nervous system (CNS) metastases, were enrolled into 1 of 5 ALK+ cohorts dependent on the number of prior TKIs received, and 1 ROS1+ cohort with no restriction on the extent of previous therapy. Pts received lorlatinib 100 mg QD. The primary objective was overall and intracranial (IC) antitumor activity, measured as confirmed overall and IC response by independent central review (ICR). Results: At the data cutoff (15 Aug 2016), 65 pts with ALK+ NSCLC were treated with ≥1 prior 2nd-generation TKI (alectinib, ceritinib, brigatinib, or other). Of these pts, 41 had CNS metastases at baseline. The table shows the confirmed overall and IC responses (complete response +partial response) by ICR. The most common treatmentrelated adverse events (TRAEs) of any grade in pts who received prior ALK TKIs were hypercholesterolemia, hypertriglyceridemia, and peripheral neuropathy. Hyperlipidemia was successfully managed by appropriate medical treatment. Conclusions: Lorlatinib has shown clinical activity in pts with ALK+ NSCLC who had received ≥1 prior 2nd-generation TKI. (Table Presented).