Takeda’s Alunbrig (brigatinib) has shown promise in treating ALK-positive metastatic non-small cell lung cancer (NSCLC) patients who either progressed with — or could not tolerate treatment with — Xalkori (crizotinib).
Findings of this work were published in the study, “Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial,” in the Journal of Clinical Oncology.
The Phase 2 ALTA trial (NCT02094573) enrolled 222 patients with either locally advanced or metastatic lung cancer. Patients were treated with an oral 90-mg dose of Alunbrig, once daily. After seven days, about half of the group continued on 180 mg, while the remaining patients continued receiving the 90-mg dose. Patients were followed for a median of eight months.
The analysis carried out by an independent review committee indicated that patients in the higher-dose group had an overall response rate of 53%. Also, 67% of patients with brain metastases positively responded to treatment in the higher-dose group.
Five patients in the higher-dose group and four in the lower-dose group had a complete response. In both groups, the median duration of response lasted more than a year.
“Given that half of ALK+ NSCLC patients treated with crizotinib will progress within one year, in many cases with cancer spreading to the brain, it is critical that we have new effective therapies that can address these mechanisms of resistance,” Dong-Wan Kim, MD, PhD, and principal research in the trial, said in a news release. “The ALTA trial results offer clinicians important information on the efficacy and safety of brigatinib in patients who have progressed on crizotinib, and show brigatinib to be highly effective in this setting, both systemically and in the brain.”
Japan-based Takeda announced that the U.S. Food and Drug Administration has granted accelerated approval to Alunbrig, a tyrosine kinase inhibitor that works by blocking the action of enzymes called tyrosine kinases, which are highly active in certain cancers. Common side effects reported in the trial included gastrointestinal symptoms (nausea, diarrhea), headache, and cough. The most frequently experienced adverse side effects included hypertension, pneumonia, and increase in certain metabolic enzymes.
Pulmonary adverse events with early onset occurred in 6% of all patients, but no such events occurred after a dosage increase to 180 mg (in the higher-dosage group).
The ALTA trial’s safety report supports the use of Alunbrig in 180-mg doses, once daily, in future clinical trials.
“The publication of the Phase 2 ALTA trial results is an important milestone for the brigatinib clinical program, and we thank the patients, their families and caregivers, and the investigators for their participation in and dedication to this trial,” said David Kerstein, MD, and the study’s author. “We look forward to sharing additional ALUNBRIG data from our studies as we continue to develop the drug to address the unmet medical needs of patients with ALK+ NSCLC.”