LBA7 - A randomized, double-blind, multinational phase III study to assess the efficacy and safety of lazertinib versus gefitinib in the first-line treatment of patients with EGFR mutation (EGFRm), advanced NSCLC (LASER301; NCT04248829)

Background

Lazertinib is a potent, CNS-penetrant, mutant-selective, and third-generation EGFR TKI targeting both EGFR T790M and sensitizing mutations while sparing wild-type EGFR. Previous clinical data suggest lazertinib may be effective as initial therapy for EGFRm advanced NSCLC.

Methods

Eligible patients (pts): ≥18 years, EGFRm (Ex19del/L858R) advanced NSCLC, and no prior EGFR-TKI/systemic anti-cancer therapy. Neurologically stable pts with CNS metastases were allowed, provided any definitive treatment/steroids was completed for ≥2 weeks. Pts were randomized 1:1 to lazertinib 240 mg once daily (qd) orally (po) or gefitinib 250 mg qd po, stratified by mutation status and race. Primary endpoint: PFS by RECIST v1.1, by investigator. DCO: 29 July 2022.

Results

A total of 393 pts were randomly assigned to blinded study treatment across 96 sites in 13 countries (196 to lazertinib and 197 to gefitinib). The median PFS was significantly longer with lazertinib than with gefitinib (20.6 months (mos) vs. 9.7 mos; HR for disease progression or death, 0.45; 95% confidence interval [CI], 0.34 to 0.58; P<0.001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The median PFS was 20.6 mos vs. 9.7 mos among Asian and NR vs. 9.7 mos among non-Asian, 20.7 mos vs 10.9 mos in Ex19del mutation and 17.8 mos vs 9.6 mos in L858R mutation for lazertinib and gefitinib, respectively. The ORR was 76% in both groups (OR, 0.99; 95% CI, 0.62 to 1.59). The median duration of response was 19.4 mos (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 mos (95% CI, 6.9 to 10.9) with gefitinib. Data on overall survival were immature at the interim analysis (29% maturity). The survival rate at 18 mos was higher with lazertinib (80%; 95% CI, 74 to 86) than gefitinib (72%; 95% CI, 65 to 78) (HR for death, 0.74; 95% CI, 0.51 to 1.08; P = 0.116). The observed safety of lazertinib and gefitinib were consistent with their previously reported safety profiles.

Conclusions

Lazertinib demonstrated significant improvement in efficacy compared to gefitinib in the front-line treatment of EGFRm advanced NSCLC, with a comparable safety profile.

Clinical trial identification

NCT04248829.

Editorial acknowledgement

Legal entity responsible for the study

Yuhan Corporation.

Funding

Yuhan Corporation.

Disclosure

B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Invited Speaker: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi; Other, Personal, Other, Founder: DAAN Biotherapeutics. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Takeda, MSD, YUHAN, Amgen, Alpha Pharmaceutical, Janssen, BMS, Roche, Daichi Sankyo. J.H. Kang: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Merck, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Roche, MSD, Ono, YUHAN, Takeda, YuHAN; Financial Interests, Personal, Research Grant: Ono, Daiichi Sankyo, Boehringer Ingelheim. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Takeda, Yuhan; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Other, Conference sponsorship: Taiho; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim. T. Baisamut (reungwetwattana): Financial Interests, Personal, Advisory Board, and speaker: Astrazeneca, Pfizer, Roche, MSD, Novartis, BMS, Amgen; Financial Interests, Personal, Advisory Board: Yuhan; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Novartis, MSD. J.C. Yang: Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: Astrazeneca, Boehringer Ingelheim, Novartis, Astrazeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Personal, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Personal, Member: ASCO. I. Cicin: Other, Personal, Other, Principal investigator for Jounce Therapeutic: Jounce Therapeutic. D. Kim: Financial Interests, Personal, Invited Speaker: Korean Cancer Association, Korean Society of Medical Oncology, Korean Association for Lung Cancer, Taiwan Lung Cancer Society, Japan Cancer Association; Financial Interests, Personal, Other, Scientific Advisor: HEALTH INSURANCE REVIEW & ASSESSMENT SERVICE, Korea; Financial Interests, Personal, Invited Speaker, Medical writing assistance: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Chong Keun Dang, Daiichi-Sankyo, GSK, Pfizer, MSD, Merck, Novartis, Roche, Takeda, Yuhan; Financial Interests, Institutional, Invited Speaker, Clinical Trial Funding: Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Merus, MIrati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge BioTherapeutics, GSK; Financial Interests, Institutional, Research Grant, Laboratory research funding to my institution: InnoN; Non-Financial Interests, Personal, Advisory Role: Amgen, BMS / ONO Pharmaceuticals, Daiichi Sankyo, Janssen, GSK, Pfizer, AstraZeneca, SK Biopharm, Takeda, Yuhan; Non-Financial Interests, Personal, Invited Speaker: Korean Cancer Association, Korean Society of Medical Oncology, Korean Association for Lung Cancer, Asian Thoracic Oncology Research Group; Other, Personal, Other, Travel support for advisory board meeting attendance: Amgen, Daiichi-Sankyo; Other, Personal, Other, Clinical trial research funding to my institution: Asian Thoracic Oncology Research Group. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AdtraZeneca, Prizer, Boehringer lngelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co.Ltd, Roche; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Roche, Hansoh, BeiGene, Lilly Suzhou Pharmaceutical Co.Ltd. K.H. Lee: Financial Interests, Personal, Advisory Board: BMS, MSD, Eli Lilly, Yuhan, Pfizer, AstraZeneca; Financial Interests, Personal, Funding: Merck. Y. Pang: Non-Financial Interests, Personal, Principal Investigator, LAZER301 Trial: Yuhan Corporation. A. Zimina: Non-Financial Interests, Personal, Principal Investigator, Participation as PI in YUHAN LASER-301 trial.: YUHAN. C.H. Fong: Financial Interests, Personal, Invited Speaker, Investigator fees: Yuhan Corporation, Janssen Research & Development, LLC, Arcus Biosciences, Inc., Novartis Pharmaceuticals, Hoffmann-La Roche. E. Poddubskaya: Financial Interests, Institutional, Principal Investigator: Yuhan Corporation. Y. Kim: Financial Interests, Personal, Full or part-time Employment, Clinical research physician and medical monitor: Yuhan Corporation. T. An: Financial Interests, Personal, Full or part-time Employment: Yuhan Cooperation. H. Lee: Financial Interests, Personal, Full or part-time Employment: Yuhan. H. Byun: Financial Interests, Personal, Full or part-time Employment: Yuhan Corporation. B. Zaric: Financial Interests, Personal, Invited Speaker, invited speaker, ADB, expert testimony: Roche; Financial Interests, Personal, Advisory Board, invited speaker, ADB, expert testimony: AstraZeneca, Pfizer, MSD, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals.