Safety and Efficacy of Lorlatinib (PF-06463922) from the Dose-Escalation Component of a Study in Patients with Advanced ALK+ or ROS1+ Non-Small Cell Lung Cancer (NSCLC).

9009Background: Most patients (pts) with anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) NSCLC develop resistance to tyrosine kinase inhibitor (TKI) therapy, with the central nervous system (CNS) as a common site of relapse. Lorlatinib is a selective brain-penetrant ALK/ROS1 TKI active against most known resistance mutations. Methods: In Ph. I of the ongoing Ph. I/II study NCT01970865, eligible pts had ALK+ or ROS1+ NSCLC with/without brain metastases (mets) and were treatment naive or had disease progression after ≥1 TKIs. Pts received lorlatinib on day –7 and daily from day 1. Primary objective was to identify the MTD and recommended Ph. II dose (RP2D). Other objectives were safety and efficacy by RECIST v1.1, including intracranial activity. Results: Of 54 pts treated in Ph. I as of Nov 30 2015, 41 were ALK+, 12 ROS1+; and 1 with mutation status not recorded at cut-off date. Pts were heavily pretreated:27 had received >1 prior TKI, 20 1 prior TKI and 7 were TKI naive; 39 pts had CNS mets a...