ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the initiation of a pivotal global Phase 2 trial of AP26113 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who were previously treated with crizotinib. The ALTA ( ALK in Lung Cancer Trial of AP26113) trial is designed to determine the safety and efficacy of AP26113 in refractory NSCLC patients who test positive for the anaplastic lymphoma kinase (ALK+) oncogene.
“Preliminary data from more than 120 patients studied thus far in the ongoing Phase 1/2 trial have provided important insights into the safety and efficacy of AP26113 and its profile at different dose levels,” said Frank G. Haluska, M.D., Ph.D., senior vice president of clinical research and development and chief medical officer at ARIAD. “We anticipate that the Phase 2 ALTA trial will give us the opportunity to further substantiate these encouraging findings and, importantly, to study two distinct doses of AP26113, which will allow for the potential to optimize its activity in patients with brain metastases.”
Trial Design and Statistical Analysis
Approximately 220 patients with ALK+ NSCLC who have been treated with and progressed on their most recent crizotinib therapy will be randomized one-to-one to receive either 90 mg of AP26113 once per day (QD) continuously, or a lead-in dose of 90 mg QD for seven days followed by 180 mg QD continuously.The primary endpoint of the ALTA trial will be objective response rate (ORR) as measured by RECIST criteria. Secondary endpoints include time to response, duration of response, disease control rate, progression-free survival, overall survival, safety, and tolerability. Health related quality of life will also be assessed. In patients who have active brain metastases, central nervous system response will also be measured. The ALTA trial will be conducted in patients with advanced NSCLC who have ALK rearrangement documented by fluorescence in situ hybridization (FISH). The trial will be randomized to independently examine the overall response rate for each dose level. Patients will be stratified by response to prior therapy and by the presence or absence of active brain metastases. The study is designed to have approximately a 90% power to rule out an uninteresting ORR of 20%, when the true rate is 35% or higher. “Although crizotinib is effective in metastatic ALK-positive NSCLC, patients still progress, on average within a year, and often, that progression is in the brain,” said D. Ross Camidge, M.D., Ph.D., associate professor of medicine at University of Colorado School of Medicine. “AP26113 has already shown activity in post-crizotinib patients with ALK-positive NSCLC, including some patients with brain metastases. The ALTA trial will evaluate AP26113 in a larger population of ALK+ patients with acquired resistance to crizotinib. This will be a great opportunity to assess the safety and efficacy of two dose levels of this promising investigational drug in more detail, particularly in patients with active brain metastases.”