2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Phase 2 study of brigatinib in patients (pts) with anaplastic lymphoma kinase (ALK)−positive, advanced non–small cell lung cancer (NSCLC) that progressed on alectinib or ceritinib.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #437b)
J Clin Oncol 37, 2019 (suppl; abstr TPS9115)
Author(s): Edward S. Kim, Sai-Hong Ignatius Ou, Fabrice Barlesi, Tony S. K. Mok, Myung-Ju Ahn, Veronica Bunn, Pingkuan Zhang; Levine Cancer Institute, Atrium Health, Charlotte, NC; Chao Family Comprehensive Cancer Center, University of California, Irvine School of Medicine, Orange, CA; Aix Marseille University, INSERM, CNRS, CRCM, APHM, CEPCM CLIP2, Marseille, France; Prince Wales Hospital, Shatin, China; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA
Background: Second-generation ALK tyrosine kinase inhibitors (TKIs) alectinib and ceritinib have demonstrated efficacy and acceptable safety in ALK TKI-pretreated and TKI-naive NSCLC. However, as with crizotinib, resistance to alectinib and ceritinib eventually develops, with secondary resistance mutations detected in approximately 50% of pts. Brigatinib is a next-generation ALK TKI designed to have potent and broad activity against ALK mutants. Post-crizotinib, brigatinib demonstrated high systemic and CNS objective response rates (ORR) and the longest reported median progression-free survival (PFS) of any ALK inhibitor in this setting (16.3–16.7 mo) (Huber. J Clin Oncol 2018;36; Bazhenova. Ann Oncol 2017;28); efficacy was demonstrated regardless of mutations. Based on nonclinical and clinical data, brigatinib may show efficacy in ALK+ NSCLC that has developed resistance or failed to respond to alectinib/ceritinib. This trial was designed to assess efficacy and safety of brigatinib in pts with ALK+ NSCLC that has progressed on alectinib or ceritinib. Methods: This is a phase 2, open-label, single-arm, multicenter, international trial (NCT03535740) in pts (≥18 y) with locally advanced/metastatic NSCLC and disease progression on alectinib or ceritinib (± prior crizotinib; ≤3 different systemic regimens for locally advanced/metastatic disease). Pts receive oral brigatinib 180 mg QD with 7-day lead-in at 90 mg QD. Treatment beyond progression or escalation to brigatinib 240 mg QD is permitted. Primary endpoint: independent review committee (IRC)−assessed confirmed ORR (cORR) per RECIST v1.1. Secondary endpoints: investigator (INV)-assessed cORR, duration of response (INV- and IRC-assessed), PFS, disease control rate, and time to response; in pts with baseline brain metastases: IRC-assessed intracranial cORR, duration of intracranial response, and intracranial PFS; OS; safety/tolerability; and HRQoL. Exploratory endpoints include biomarker analyses. The study was initiated in Dec 2018 at 78 sites (North America, Europe, Asia), with a planned sample size of 103 pts. Accrual is ongoing. Clinical trial information: NCT03535740