5751 - Phase 3 ALTA-3 study of brigatinib (BRG) vs alectinib (ALC) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)−positive non–small cell lung cancer (NSCLC) that progressed on crizotinib (CRZ)

Background

The second-generation ALK tyrosine kinase inhibitor (TKI) ALC has demonstrated efficacy and acceptable safety in ALK+ NSCLC pts who have progressed on CRZ. However, resistance to ALC eventually develops, with secondary resistance mutations detected in approximately 50% of pts and a median progression-free survival (PFS) <1 year. BRG is a next-generation ALK TKI designed to have potent and broad activity against ALK mutants. Post-CRZ, BRG demonstrated high systemic and central nervous system (CNS) objective response rates (ORRs) and the longest reported median PFS of any ALK inhibitor in this setting (16.3–16.7 mo) (Huber. J Clin Oncol 2018;36; Bazhenova. Ann Oncol 2017;28). The current trial was designed to compare efficacy and safety of BRG vs ALC in pts with ALK+ NSCLC that has progressed on CRZ.

Trial design

The second-generation ALK tyrosine kinase inhibitor (TKI) ALC has demonstrated efficacy and acceptable safety in ALK+ NSCLC pts who have progressed on CRZ. However, resistance to ALC eventually develops, with secondary resistance mutations detected in approximately 50% of pts and a median progression-free survival (PFS) <1 year. BRG is a next-generation ALK TKI designed to have potent and broad activity against ALK mutants. Post-CRZ, BRG demonstrated high systemic and central nervous system (CNS) objective response rates (ORRs) and the longest reported median PFS of any ALK inhibitor in this setting (16.3–16.7 mo) (Huber. J Clin Oncol 2018;36; Bazhenova. Ann Oncol 2017;28). The current trial was designed to compare efficacy and safety of BRG vs ALC in pts with ALK+ NSCLC that has progressed on CRZ.Table:

1586TiP

Clinical trial identification

NCT03596866.

Editorial acknowledgement

Peloton Advantage, LLC, an OPEN Health Company; funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Funding

ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Disclosure

S. Popat: Research grant / Funding (institution): Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria (self): Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Advisory / Consultancy: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel / Accommodation / Expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. G. Liu: Research grant / Funding (institution): Takeda, AstraZeneca, Roche, Bayer, Boehringer Ingerheim; Honoraria (self): Roche, Takeda, AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Merck,Novartis, EMD Serano, Bayer; Advisory / Consultancy: Roche, Novartis, Pfizer. S. Lu: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, Roche, JS InnoPharm; Speaker Bureau / Expert testimony: AstraZeneca, Roche; Research grant / Funding (self): AstraZeneca, Hutchison MediPharma. G. Song: Full / Part-time employment: Takeda. V. Samnotra: Full / Part-time employment: Takeda. J.C. Yang: Advisory / Consultancy: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, Daiichi Sankyo, Takeda, AstraZeneca, Hansoh Pharmaceuticals.