Abstract
Introduction: This integrated analysis of a phase 1/2 study (NCT03046992) evaluated the efficacy and safety of lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive NSCLC after previous EGFR TKI therapy. Methods: Adults with EGFR mutation-positive NSCLC that progressed after prior EGFR-directed TKIs received once daily oral lazertinib 240 mg continuously until disease progression. Prior TKIs to treat T790M-positive NSCLC were prohibited. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included progression-free survival, overall survival, and intracranial ORR. Results: A total of 78 patients received lazertinib 240 mg at 17 centers in South Korea. Among patients with T790M-positive tumors at baseline (N = 76), one (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% confidence interval [CI]: 44.1–66.4). Median progression-free survival was 11.1 months (95% CI: 5.5–16.4). Median overall survival was not reached (median follow-up = 22.0 mo). In patients with measurable intracranial lesions (n = 7), one (14.3%) had a complete intracranial response and five (71.4%) had partial responses, giving an intracranial ORR of 85.7% (95% CI: 59.8%–100.0%). The most common treatment-emergent adverse events were rash (37.2%), pruritus (34.6%), and paresthesia (33.3%); most were mild to moderate in severity. Serious drug-related adverse events occurred in three patients (gastritis, pneumonia, pneumonitis). The major mechanism of resistance was EGFR T790M loss. Conclusions: Lazertinib 240 mg/d has a manageable safety profile with durable antitumor efficacy, including brain metastases, in patients with advanced T790M-positive NSCLC after previous EGFR TKI therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 558-567 |
| Number of pages | 10 |
| Journal | Journal of Thoracic Oncology |
| Volume | 17 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2022 Apr |
Bibliographical note
Funding Information:Disclosure: Dr. B.C. Cho reported receiving research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan Corporation, Ono Pharmaceutical, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corporation; receiving royalties from Champions Oncology; serving as a consultant for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono Pharmaceutical, Yuhan Corporation, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Medpacto, and Blueprint Medicines; participating in Scientific Advisory Boards for Kanaph Therapeutics, BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, and Joseah Biopharma; serving on the Board of Directors for Interpark Bio Convergence Corporation and Gencurix Inc.; having stock ownership for TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics, Cyrus Therapeutics, and Interpark Bio Convergence Corporation; and being a founder of DAAN Biotherapeutics. Dr. J.Y. Han reported receiving research grants from Roche, Pfizer, Ono Pharmaceutical, and Takeda; receiving honoraria from Roche, AstraZeneca, and Takeda; and serving in an advisory role for AstraZeneca, Lilly, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, and Medpacto. Dr. K.H. Lee reported receiving honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Pfizer and Eli Lilly. Dr. D.W. Kim reported receiving research funding (institution), provision of medical writing services and article processing charges from Yuhan Corporation; research funding (institution) from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Chong Keun Dang, BridgeBio Therapeutics, and GlaxoSmithKline; and travel support for Advisory Board meeting attendance from Amgen and Daiichi Sankyo. Dr. J.S. Ahn reported receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events, and participation on a Data Safety Monitoring Board or Advisory Board for Yuhan Corporation. Dr. Y. Lee reported receiving consulting fees from Roche Korea and Yuhan Corporation. Dr. D.H. Lee reported receiving personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CJ Healthcare, Eli Lilly, ChongKeunDang, Janssen, Merck, Merck Sharp & Dohme, Munipharma, Novartis, Ono Pharmaceutical, Pfizer, Roche, Samyang Biopharm, ST Cube, AbbVie, Takeda, Genexine, Menarini, and BC Pharma; and nonfinancial support from Takeda and Blueprint Medicine. Ms. J.A. Kang is a salaried employee of Yuhan Corporation and reports having stock interests in Yuhan Corporation. Ms. N. Lee is a salaried employee of Yuhan Corporation. Dr. M.J. Kwon is a salaried employee of Yuhan Corporation and reports having stock interests in Yuhan Corporation. Ms. C. Espenschied reports having stock or stock options from Guardant Health. Dr. A. Yablonovitch reports receiving support for attending meetings and/or travel, patents (planned, issued, or pending), and stock or stock options from Guardant Health. Dr. M.-J. Ahn reports receiving grants or contracts from AstraZeneca; receiving consulting fees from AstraZeneca, Merck Sharp & Dohme, Novartis, Takeda, Eli Lilly, Ono Pharmaceutical, Roche, Yuhan Corporation, and Alpha Pharmaceuticals; receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Merck Sharp & Dohme, Novartis, Takeda, Lilly, Ono Pharmaceutical, Roche, Yuhan Corporation, Amgen, Merck, BeiGen, and Alpha Pharmaceuticals; and having participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Merck Sharp & Dohme, Novartis, Takeda, Lilly, Ono Pharmaceutical, Roche, Yuhan Corporation, Amgen, Merck, BeiGen, and Alpha Pharmaceuticals. The remaining authors declare no conflict of interest.The authors thank the patients and their families and the staff and investigators at all study sites. Medical writing and editorial support was provided by Lee Miller, BSc (Hons), and Harriet Lamb, BSc (Hons), of Miller Medical Communications Ltd. UK, and was funded by Yuhan Corporation. LASER201 Parts A, B, and C were sponsored by Yuhan Corporation and Korea Drug Development Fund funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (KDDF-201803-05, Republic of Korea). Yuhan Corporation was responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication. Deidentified participant data will be made available when all endpoints of all trial have been evaluated. Any requests for trial data and supporting material (data dictionary and statistical analysis plan) will be reviewed by the trial management group in the first instance. Only requests that have a methodologically sound proposal and whose proposed use of the data has been approved by the independent trial steering committee will be considered. Proposals should be directed to the corresponding author in the first instance; to gain access, data requestors will need to sign a data access agreement.
Funding Information:
The authors thank the patients and their families and the staff and investigators at all study sites. Medical writing and editorial support was provided by Lee Miller, BSc (Hons), and Harriet Lamb, BSc (Hons), of Miller Medical Communications Ltd., UK, and was funded by Yuhan Corporation. LASER201 Parts A, B, and C were sponsored by Yuhan Corporation and Korea Drug Development Fund funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (KDDF-201803-05, Republic of Korea). Yuhan Corporation was responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication.
Publisher Copyright:
© 2021 International Association for the Study of Lung Cancer
All Science Journal Classification (ASJC) codes
- Oncology
- Pulmonary and Respiratory Medicine