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
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract