Higher Dose of Alunbrig Approved to Treat Lung Cancer

Alunbrig (brigatinib) was granted a supplemental new drug application for the treatment of patients with non-small cell lung cancer (NSCLC). Now, the drug can be administered via 180-mg tablets.

In April 2017, the FDA granted an accelerated approval to Alunbrig as a treatment for patients with metastatic ALK-positive NSCLC who are resistant to prior Xalkori (crizotinib). Alunbrig is approved at a starting dose of 90 mg once daily for seven days. Patients who tolerate the initial regimen have their dose increased to 180 mg once daily. Previously, Alunbrig was only available in 30- and 90-mg tablets.

“Today’s approval of the Alunbrig 180 mg tablets will reduce pill burden for patients taking Alunbrig for advanced ALK-positive NSCLC,” Mohammad Jahanzeb, M.D., Professor of Clinical Medicine, Hematology and Oncology at University of Miami's Miller School of Medicine, said in a statement. “As a physician, having a 180-mg tablet available for my patients may help them better manage their treatment schedule.”

The approved regimen of Alunbrig is based on findings from the ongoing 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 (112 patients) or 180 mg daily with a seven-day lead in period at 90 mg per day (110 patients). 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 duration of response was 13.8 months in both arms.

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 one-year PFS rate was 39 percent with the 90-mg dose and 54 percent in the 180-mg arm.

The one-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 (18 patients), the intracranial ORR was 67 percent. In those with brain metastases treated with the 90-mg dose (26 patients), the intracranial ORR was 42 percent.

The median intracranial duration of response was not estimable in the 90-mg arm and was 5.6 months among patients receiving 180 mg. In the group achieving an intracranial response, the response lasted for at least four months in 78 percent and 68 percent of patients in the 90- and 180-mg arms, respectively.

The most common all-grade treatment-emergent adverse events (AEs) in the 90 mg and 180 mg arms, respectively, were nausea (40 percent and 33 percent), diarrhea (38 percent and 19 percent), cough (34 percent and 18 percent) and headache (27 percent and 28 percent). The most common grade 3 or higher treatment emergent AEs in the 90 mg and 180 mg arms, respectively, were increased blood creatinine phosphokinase (3 percent and 9 percent) and hypertension (6 percent each).

There was a subset of patients (6 percent) who experienced early onset pulmonary AEs, which occurred within a median of two days (range, 1-9). 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 180 mg and 90 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.

Takeda, the manufacturer of Alunbrig, reported in a press release that updated data from the ALTA trial will be presented at the 18th World Conference on Lung Cancer, being held Oct. 15 to 18 in Yokohama, Japan.