General Information

Alunbrig (brigatinib) is a kinase inhibitor.

Alunbrig is specifically indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval.

Alunbrig is specifically indicated for the first line treatment of adult patients with ALK+ metastatic NSCLC, as detected by an FDA-approved test.

Alunbrig is supplied as a tablet for oral administration. The recommended dosing regimen is 90 mg orally once daily for the first 7 days. If 90 mg is tolerated during the first 7 days, increase the dose to 180 mg orally once daily. Administer Alunbrig until disease progression or unacceptable toxicity. If Alunbrig is interrupted for 14 days or longer for reasons other than adverse reactions, resume treatment at 90 mg once daily for 7 days before increasing to the previously tolerated dose. Alunbrig may be taken with or without food. Instruct patients to swallow tablets whole. Do not crush or chew tablets. If a dose of Alunbrig is missed or vomiting occurs after taking a dose, do not administer an additional dose and take the next dose at the scheduled time.

Clinical Results

FDA Approvals

The FDA approval of Alunbrig was based on a two-arm, open-label, multicenter trial (ALTA) in adult patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who had progressed on crizotinib. The major efficacy outcome measure was confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by an Independent Review Committee (IRC). A total of 222 patients were randomized to receive either 90 mg once per day (QD) continuously (Arm A), or a lead-in dose of 90 mg QD for seven days followed by 180 mg QD continuously (Arm B). Randomization was stratified by brain metastases (present versus absent) and best prior response to crizotinib (complete or partial response versus any other response/unevaluable). The median follow-up was 8.3 months in Arm B and 7.8 months in Arm A. Investigator-assessed confirmed ORR in Arm B was 54%. IRC-assessed confirmed ORR in Arm B was 53%. Investigator-assessed confirmed ORR in Arm A was 45% and IRC- assessed confirmed ORR in Arm A was 48%. The Investigator-assessed median PFS was 12.9 months and 9.2 months in Arm B and Arm A, respectively. The IRC-assessed median PFS was 15.6 months and 9.2 months in Arm B and Arm A, respectively.

Mechanism of Action

Alunbrig (brigatinib) is a kinase inhibitor with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice.