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
Lazertinib, a 3rd generation EGFR-TKI, in patients with EGFR-TKI resistant NSCLC: Updated results of phase I/II Study.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #360)
J Clin Oncol 37, 2019 (suppl; abstr 9037)
Author(s): Myung-Ju Ahn, Ji-Youn Han, Sang-We Kim, Ki Hyeong Lee, Dong-Wan Kim, Yun-Gyoo Lee, Eun Kyung Cho, Gyeong-won Lee, Jong-Seok Lee, Joo-Hang Kim, Jin-Soo Kim, Young Joo Min, Sung Sook Lee, Sang Won Shin, HyeRyun Kim, Min Hee Hong, Jin Seok Ahn, Seoung Oh Lee, Sohee Kim, Byoung Chul Cho; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea; University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea; Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea; Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea; Gyeongsang National University Hospital, Jinju, South Korea; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; CHA Bundang Medical Center, CHA University, Seongnam, South Korea; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea; Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea; Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; Yuhan Research Institute, Yuhan Corporation, Yongin, South Korea; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
Background: Lazertinib (YH25448) is a highly mutant-selective, irreversible 3rd-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the activating EGFR mutations (Del19 and L858R), as well as the T790M mutation, while sparing wild type. We report the updated results from a Phase I/II study of lazertinib (NCT03046992). Methods: Patients with advanced and metastatic NSCLC who had progressed after treatment with standard EGFR-TKIs with/without asymptomatic brain metastases (BM) were enrolled in an open-label, multicenter, phase I/II study with dose-escalation and expansion cohorts. Lazertinib was administered once daily at doses between 20 to 320 mg in a 21-day cycle. Patients were assessed for safety, tolerability and efficacy. T790M mutation was required in the dose-expansion cohorts. Results: As of 26 Nov 2018, a total of 127 patients were enrolled. The dose-escalation cohort included 38 patients administered with 20 to 320 mg across 7 dose levels, and 89 patients in the dose-expansion cohort were administered with 40 to 240 mg across 5 dose levels. No dose-limiting toxicities were observed. The median duration of treatment was 9.7 months and 58 patients are still ongoing. The objective response rate (ORR) was 60% in all patients, 64% in T790M+ patients, and 37% in T790M- patients by investigators assessment. In BM patients with measurable lesion (n = 14), the intracranial ORR was 50%. The median progression-free survival (PFS) was 8.1 months in all patients, 9.5 months in T790M+ patients, and 5.4 months in T790M- patients. Subgroup analysis showed that ORR was 65% and PFS was 12.2 months in T790M+ patients with ≥ 120 mg (n = 62). The most common treatment-emergent adverse events (TEAEs) were pruritus (27%), rash (24%), constipation (20%), decreased appetite (19%) and diarrhea (14%). TEAEs leading to dose discontinuation were observed in 3% of patients. Drug related TEAEs of grade ≥ 3 was observed in 3% of the patients. Conclusions: Lazertinib was safe, well-tolerated and exhibits promising systemic and intracranial antitumor activity in EGFR T790M+ NSCLC patients. Dose extension cohorts in the 1st and 2nd line settings are underway at 240 mg dose. Clinical trial information: NCT03046992