Abstract 5751
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
Primary Endpoint |
Blinded independent review committee (BIRC)−assessed PFS per RECIST v1.1 |
Secondary Endpoints |
BIRC-assessed intracranial PFS Overall survival Investigator- and BIRC-assessed ORR, time to response, and duration of response (DOR) BIRC-assessed intracranial ORR and DOR Safety/tolerability Health-related quality of life |
Selected Exploratory Endpoints |
BIRC-assessed CNS efficacy per Response Assessment in Neuro-Oncology Brain Metastases criteria (intracranial ORR, DOR, and PFS) Molecular determinants of efficacy and safety with BRG and ALC |
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.
Resources from the same session
5823 - Pulmonary tumor-draining vein exosomal lincRNA-p21 levels impacts non-small cell lung cancer prognosis
Presenter: Joan Castellano
Session: Poster Display session 1
Resources:
Abstract
1842 - Immunological impact of surgery in NSCLC patients
Presenter: Akitoshi Yanagihara
Session: Poster Display session 1
Resources:
Abstract
4124 - The prognostic value of selected immunological panel in predicting the prognosis of early-stage resectable non-small cell lung cancer
Presenter: Sha Zhao
Session: Poster Display session 1
Resources:
Abstract
4468 - Genomic Heterogeneity and Clonality Analysis of Multiple synchronous lung cancers (MSLCs)
Presenter: Fachen Zhou
Session: Poster Display session 1
Resources:
Abstract
5547 - Analysis of immunosuppressive factors produced by tumorspheres in NSCLC. Prognostic value of Galectin-3 in adenocarcinoma
Presenter: Susana Torres Martinez
Session: Poster Display session 1
Resources:
Abstract
1658 - Frequency of epidermal growth factor receptor (EGFR) mutations in stage IB–IIIA EGFR mutation positive non-small-cell lung cancer (NSCLC) after complete tumour resection
Presenter: Masahiro Tsuboi
Session: Poster Display session 1
Resources:
Abstract
1535 - EGFR mutation is not a prognostic factor in completely resected lymph node–negative pulmonary adenocarcinoma (LNNPA)
Presenter: Nussara Leeladejkul
Session: Poster Display session 1
Resources:
Abstract
3262 - Prognostic significance of elements of the adaptive immunity in the microenvironment of early-stage non small cell lung cancer
Presenter: Aliki Liakea
Session: Poster Display session 1
Resources:
Abstract
4643 - Combined immunoscore for prognostic stratification of early stage NSCLC patients
Presenter: Giulia Pasello
Session: Poster Display session 1
Resources:
Abstract
4819 - Radiation-induced lung injury and misdiagnosis rate after SBRT
Presenter: Xiaolong Fu
Session: Poster Display session 1
Resources:
Abstract