Regulatory Decision Summary for Alunbrig

A multicenter, randomized, open label, phase III (ALTA 1) study was submitted to support the use of Alunbrig (brigatinib) as a 1^st line treatment for patients with ALK-positive locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC). Two hundred and seventy five patients were randomized in a 1:1 ratio to receive brigatinib 180 mg once daily, with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib 250 mg orally twice daily (n = 138).  Randomization was stratified by the presence or absence of brain metastases and prior chemotherapy use for locally advanced or metastatic disease. The primary endpoint of this pivotal trial was Progression Free Survival (PFS). The key secondary endpoints were Objective Response Rate (ORR) and intracranial ORR, assessed by the blinded independent review (BIRC).

The study met its primary objective and demonstrated that median PFS was improved from 11.0 months (95% confidence interval [CI]: 9.2, 12.9) to 24.0 months (95% CI: 18.5, NE) with a HR of 0.49 (p <0.0001). The key secondary endpoint of ORR was also improved by approximately 10%, with brigatinib 73.7% (95% CI: 65.5; 80.9) compared to crizotinib 61.6% (95% CI: 52.9; 69.7). The BIRC intracranial ORR results (77.8% with brigatinib vs 26.1% with crizotinib) are considered supportive of the primary endpoint and also demonstrate a clinically relevant treatment effect.

With a median exposure of approximately 2 years, the safety profile of brigatinib for use in 1^st line treatment was consistent with that from the approved 2^nd line treatment. No new safety issues have been raised. The adverse events are clinically manageable.

The overall benefit-risk profile of Alunbrig was deemed to be positive for use as monotherapy in the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.