ARIAD Pharmaceuticals recently announced the start of a Phase 3 clinical trial of brigatinib for locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults with mutations in the anaplastic lymphoma kinase (ALK) – a tumor-promoting gene. If approved by the FDA, the treatment is expected to become a new first-line treatment for NSCLC.
Brigatinib is an ALK blocker developed by Cambridge, Massachusetts-based ARIAD, which in 2014 received Breakthrough Therapy designation from the FDA, a label reserved for drug candidates where preliminary clinical evidence indicates the drug may provide considerable improvement over existing therapies for serious or life-threatening diseases.
The trial, called ALTA-1L, will be open to adults with stage 3B or stage 4 NSCLC who have not previously been treated with an ALK blocker. The drug will be compared to crizotinib (an anti-cancer drug) on an open-label basis, and the efficacy of the treatment will be measured by progression-free survival. The multicenter trial will involve about 150 sites in North America, Europe, and the Asia-Pacific region.
The team plans to enroll 270 patients, who will receive either brigatinib or crizotinib. ARIAD expects to complete patient enrollment in 2018.
“We are pleased to be advancing brigatinib into a pivotal Phase 3 trial as a potential new therapy for patients with ALK+ NSCLC, who have not yet received an ALK inhibitor,” said Tim Clackson, president of research and development and chief scientific officer of ARIAD, in a press release. “We believe that the encouraging results shown in our preclinical and ongoing Phase 1/2 studies suggest brigatinib has the potential to improve outcomes for ALK+ NSCLC patients as compared to treatment with crizotinib.”
Secondary endpoints of the trial include safety and tolerability, overall survival, quality of life, and other measures of response.
“This head-to-head study will directly test brigatinib against crizotinib in the TKI-naïve ALK+ setting – where innovative therapies are needed to improve response rates and to delay progression that can occur through the emergence of secondary resistance mutations in ALK and progression in the central nervous system,” said D. Ross Camidge, director of thoracic oncology at the University of Colorado. “In patients who have experienced crizotinib failure, brigatinib has already exhibited very impressive progression-free survival and marked activity in patients with CNS [central nervous system] metastases.”