Background: In this open-label, international phase 2 study, the authors assessed the efficacy and safety of olmutinib in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who had a confirmed T790M mutation and disease progression on previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Methods: Patients aged ≥20 years received once-daily oral olmutinib 800 mg continuously in 21-day cycles. The primary endpoint was the objective response rate (patients who had a confirmed best overall response of a complete or partial response), assessed by central review. Secondary endpoints included the disease control rate, the duration of objective response, progression-free survival, and overall survival. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Results: Overall, 162 patients (median age, 63 years; women, >60%) were enrolled from 68 sites in 9 countries. At the time of database cutoff, 23.5% of enrolled patients remained on treatment. The median treatment duration was 6.5 months (range, 0.03-21.68 months). Overall, 46.3% of patients (95% CI, 38.4%-54.3%) had a confirmed objective response (all partial responses). The best overall response (the objective response rate regardless of confirmation) was 51.9% (84 patients; 95% CI, 43.9%-59.8%). The confirmed disease control rate for all patients was 86.4% (95% CI, 80.2%-91.3%). The median duration of objective response was 12.7 months (95% CI, 8.3-15.4 months). Estimated median progression-free survival was 9.4 months (95% CI, 6.9-12.3 months), and estimated median overall survival was 19.7 months (95% CI, 15.1 months to not reached). All patients experienced treatment-emergent adverse events, and 71.6% of patients had grade ≥3 treatment-emergent adverse events. Conclusions: Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M-positive non–small cell lung cancer who received previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
Bibliographical noteFunding Information:
This study was funded by Hanmi Pharmaceutical Company, Ltd.
Keunchil Park reports personal fees from Hanmi Pharmaceutical Company, Ltd, during the conduct of the study; grants from MSD Pharmaceuticals, outside the submitted work; and personal fees from AbbVie, Amgen, AstraZeneca, BluePrint Medicines, Bristol‐Myers Squibb, Boehringer‐Ingelheim, Daiichi Sankyo, Eisai, Eli Lilly, JNJ, Merck KGaA, MSD Pharmaceuticals, Puma Biotechnology, and Takeda, outside the submitted work. Pasi A. Jänne reports other support from Hanmi Pharmaceutical Company, Ltd, during the conduct of the study; grants from Boehringer‐Ingelheim, Eli Lilly, Daiichi Sankyo, Takeda Oncology, outside the submitted work; personal fees from AstraZeneca, Boehringer‐Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Ignyta, Loxo Oncology, Eli Lilly, SFJ Pharmaceuticals, Voronoi, Daiichi Sankyo, Biocartis, Novartis, Sanofi Oncology, Takeda Oncology, Mirati Therapeutics, Transcenta, Silicon Therapeutics, Syndax, Astellas, PUMA, and Revolution Medicines, outside the submitted work; and postmarketing royalties from a Dana‐Farber Cancer Center–owned patent (EGFR Mutations) licensed to Lab Corp. Dong‐Wan Kim reports grants and nonfinancial support from Hanmi Pharmaceutical Company, Ltd, during the conduct of the study; institutional grants from Alpha Biopharm, Amgen, AstraZeneca/Medimmune, Boehringer‐Ingelheim, Daiichi‐Sankyo, Janssen, Meurs, Mirati Therapeutics, MSD Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan, outside the submitted work; and nonfinancial support from Amgen and Daiichi‐Sankyo, outside the submitted work. Ji‐Youn Han reports research funding from Ono Pharmaceutical, Pfizer, Roche, and Takeda, outside the submitted work; and personal fees from AstraZeneca, Bristol‐Myers Squibb, MSD Pharmaceuticals, Roche, Eli Lilly, MSD Oncology, Novartis, Pfizer, and Takeda, outside the submitted work. Dae Ho Lee reports personal fees from AbbVie, AstraZeneca, Boehringer‐Ingelheim, Takeda, Bristol‐Myers Squibb, ChongKunDang, CJ Healthcare, Eli Lilly, Janssen, Merck, MSD Pharmaceuticals, Mundipharma, Novartis, Ono Pharmaceutical, Pfizer, Roche, Samyang Biopharm, ST Cube, GreenCross, and Genexine, outside the submitted work. Byoung Chul Cho reports research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong‐A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceutical, Dizal Pharma, MSD Pharmaceuticals, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corporation, outside the submitted work; personal fees from Novartis, AstraZeneca, Boehringer‐Ingelheim, Roche, Bristol‐Myers Squibb, Ono Pharmaceutical, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD Pharmaceuticals, Medpacto, Blueprint Medicines, TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, Cyrus Therapeutics, Interpark Bio Convergence Corp, KANAPH Therapeutic Inc, and Guardant Health, outside the submitted work; stock ownership in TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, and KANAPH Therapeutic Inc; is the founder of DAAN Biotherapeutics; receives royalties from Champions Oncology; and is a member the boards of Gencurix Inc and Interpark Bio Convergence Corporation, outside the submitted work. Yong Kek Pang reports other support from Hanmi Pharmaceutical Company, during the course of the study. Enriqueta Felip reports personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Blueprint Medicines, Boehringer‐Ingelheim, Bristol‐Myers Squibb, Eli Lilly, Glaxo‐Smith‐Kline, Janssen, Medscape, Merck KGaA, MSD Pharmaceuticals, Novartis, Roche, Peervoice, Pfizer, Prime Oncology, Puma Biotechnology, Roche, Sanofi Genzyme, Springer, Takeda, and Touchime, outside the submitted work; grants from Grant for Oncology Innovation (GOI) and Fundacion Merck Salud, outside the submitted work; and is an independent member of the board of Grifols. Hyunjin Kim, Eunhye Baek, and Young Su Noh are employees of Hanmi Pharmaceutical Company, Ltd. Ming‐Fang Wu, Jong‐Seok Lee, and Chong‐Jen Yu made no disclosures.
All Science Journal Classification (ASJC) codes
- Cancer Research