FDA Approves Alunbrig for ALK+ NSCLC

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The Food and Drug Administration has granted accelerated approval to Alunbrig (brigatinib) for metastatic ALK-positive non-small cell lung cancer (NSCLC).

The FDA has granted Alunbrig (brigatinib) an accelerated approval as a treatment for patients with metastatic ALK-positive non—small cell lung cancer (NSCLC) who are resistant to prior Xalkori (crizotinib).

The approval is based on findings from the phase 2 ALTA trial, in which the confirmed objective response rate for Alunbrig at 180 mg daily was 53 percent and the median progression-free survival (PFS) was 13.8 months.

The ALTA trial enrolled 222 patients with ALK-positive NSCLC following progression on Xalkori. Patients were randomized to receive Alunbrig at either 90 mg daily or 180 mg daily with a 7-day lead in period at 90 mg per day. Sixty-nine percent of patients had brain metastases at the time of enrollment.

The median age of patients across the study was 54 years, and ECOG performance status (PS) was primarily 0 and 1 (93 percent), with 7 percent having an ECOG PS of 2. Sixty percent of patients did not have a smoking history prior to entering the trial and 74 percent had received prior chemotherapy. Sixty-five percent of patients had experienced a complete or partial response to Xalkori.

The confirmed ORR was 48 percent in the 90-mg arm. In those who had not received prior chemotherapy, the ORR was 52 percent. In the 180-mg dose group, those who had not received chemotherapy had an ORR of 52 percent. There were four confirmed complete responses in the 180-mg arm and one in the 90-mg group.

The median PFS in the 90-mg arm was 9.2 months. There was a 45 percent reduction in the risk of progression or death with the 180-mg dose of Alunbrig versus the 90-mg dose. The 1-year PFS rate was 39 percent with the 90-mg dose and 54 percent in the 180-mg arm.

The 1-year overall survival (OS) rate was 71 percent with the 90-mg dose versus 80 percent with the larger 180 mg dose, representing a nonstatistically significant 43 percent reduction in the risk of death with the larger dose. The median OS had not yet been reached in both arms.

In those with measurable, active brain metastases treated with the 180-mg dose, the intracranial ORR was 67 percent. In those with brain metastases treated with the 90-mg dose, the intracranial ORR was 36 percent.

The most common all-grade treatment-emergent adverse events (AEs) in the 90 mg and 180 mg arms, were nausea, diarrhea, cough and headache. The most common grade 3 or higher treatment emergent AEs in the 90 mg and 180 mg arms, respectively, were increased blood creatinine phosphokinase and hypertension.

There was a subset of patients (6 percent) who experienced early onset pulmonary AEs, which occurred within a median of two days. These events occurred prior to dose escalation in the 180-mg arm. Overall, 8 percent and 3 percent of patients discontinued treatment due to AEs in the 90 mg and 180 mg arms, respectively.

The accelerated approval of Alunbrig is contingent upon results from a confirmatory trial. The phase 3 ALTA-1L study has been initiated to compare Alunbrig with Xalkori as a frontline therapy for patients with ALK-positive NSCLC. This study is assessing the 180-mg regimen of Alunbrig.