ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced updated clinical results on its investigational tyrosine kinase inhibitor (TKI), AP26113, in patients with advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial. These study results show robust anti-tumor activity of AP26113 in patients with TKI-naïve and crizotinib-resistant anaplastic lymphoma kinase positive (ALK+) NSCLC, including in patients with brain metastases after crizotinib treatment. Crizotinib is the currently available first-generation ALK inhibitor.
The updated Phase 1/2 results are being presented this morning at the European Cancer Congress (the 38th ESMO, 32nd ESTRO, 17th ECCO conference) being held in Amsterdam.
Phase 1/2 Study Design
Patients enrolled in the Phase 1 portion of the trial had advanced solid tumors that were refractory to available therapies or had no standard or curative treatment available. The objectives of the Phase 1 portion of the trial were to characterize the safety and tolerability of AP26113, pharmacokinetics, and preliminary anti-tumor activity and to determine the recommended dose for further study of AP26113. The trial used an open-label, dose-escalating design. Anti-tumor activity was determined by serial CT scans using RECIST criteria. The study identified a recommended Phase 2 dose of 180 mg administered orally once daily.The Phase 2 portion of the trial began in June 2013 and has enrolled 26 patients in the United States and Europe. This portion of the trial consists of five expansion cohorts: (1) ALK+ NSCLC treatment-naïve, (2) ALK+ NSCLC resistant to crizotinib, (3) epidermal growth factor receptor mutant (EGFRm) NSCLC resistant to one prior EGFR TKI with documented T790M secondary mutation, (4) cancers with AP26113 targets (including ALK, ROS1, and EGFR ineligible for Cohort 3), and (5) ALK+ NSCLC, either naïve or resistant to crizotinib, with active brain metastases. Ninety-one patients have been enrolled in the study at seven dose levels ( i.e., 30, 60, 90, 120, 180, 240 and 300 mg per day, administered orally). Fifty-four patients currently remain on study. “The updated results from the on-going Phase 1/2 trial show that AP26113 continues to exhibit anti-tumor activity in patients with TKI-naïve and crizotinib-resistant ALK-positive NSCLC,” stated D. Ross Camidge, M.D., Ph.D. Associate Professor of Medicine at University of Colorado School of Medicine, the study’s presenter at ESMO. “Importantly, AP26113 is active in ALK-positive brain metastases, demonstrating responses of clinically meaningful duration.”