A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors |
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| Institution: | 1. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea;2. Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea;3. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;4. Division of Medical Oncology, Department of Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea;5. Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea;6. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;7. Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea;8. CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea;9. Division of Hematology and Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea;10. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, Republic of Korea;11. Division of Medical Oncology, Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Republic of Korea;12. Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea;13. Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Bucheon, Republic of Korea;14. Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea;15. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea;p. Clinical Development Department, Yuhan Corporation, Seoul, Republic of Korea;q. Guardant Health, Inc., Redwood City, California |
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| Abstract: | IntroductionThis 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.MethodsAdults 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.ResultsA 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.ConclusionsLazertinib 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. |
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| Keywords: | Lazertinib Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) EGFR T790M-positive non-small cell lung cancer (NSCLC) |
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