Objectives: The aim of this phase 1/2 study was to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of olmutinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who had failed ≥ 1 previous line of EGFR-tyrosine kinase inhibitor (TKI) therapy. Materials and methods: Phase 1 consisted of dose-escalation and four dose-expansion parts (1: olmutinib 300 mg once daily; 2A: 800 mg once daily [EGFR T790 M mutation-positive patients]; 2B: 500 mg twice daily [EGFR T790 M mutation-positive]; 3: 800 mg once daily [EGFR T790 M mutation-negative]). In phase 2, EGFR T790 M mutation-positive patients received olmutinib 800 mg once daily. Data from expansion part 2A and phase 2 were integrated (‘pooled phase 2′). Each olmutinib cycle was 21 days. Outcomes included: tumor response, treatment-emergent adverse events (TEAEs), pharmacokinetic parameters. Results: Overall, 272 patients received at least one olmutinib dose: dose-escalation (n = 66), expansion parts (n = 165), phase 2 (n = 41). In pooled phase 2, the overall objective response rate, confirmed by independent review, was 55.1% (38/69 evaluable patients; 95% CI, 42.6–67.1). All responses were partial responses; 23 patients had stable disease. Estimated median progression-free survival was 6.9 (95% CI, 5.6–9.7) months; estimated median overall survival was not reached. The most frequent treatment-related AEs were diarrhea (59.2% of patients), pruritus (42.1%), rash (40.8%), and nausea (39.5%). Conclusion: Olmutinib showed effective clinical activity with a manageable safety profile, indicating therapeutic potential for T790M-positive NSCLC patients who have failed ≥ 1 previous line of EGFR-TKI therapy.
Bibliographical noteFunding Information:
This study was funded by Hanmi Pharmaceutical Co. Ltd. We thank the patients, their families, and the investigators for their participation in this trial. We also thank the members of the study team (Hanmi Pharmaceutical Co. Ltd). Professional medical writing assistance was provided by David Murdoch and David P. Figgitt PhD, ISMPP CMPP?, Content Ed Net, with funding from Hanmi Pharmaceutical Co. Ltd.
Dong-Wan Kim's institution has received research funding from Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan. Dae Ho Lee has received honoraria for consulting or lecturing from AbbVie, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Chong Kun Dang Pharmaceutical, CJ Healthcare, Eli Lilly, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharmaceuticals, ST Cube and Takeda. Ji-Youn Han has received honoraria from AstraZeneca, MSD and Roche, has acted in a consultancy/advisory role for AstraZeneca, BMS, Eli Lilly, MSD, Novartis, Pfizer and Takeda, and has received research funding from Pfizer and Roche. Jin-Soo Kim has stock/ownership interests in Chong Kun Dang Pharmaceutical and DEA HWA Pharmaceutical, has received honoraria from CJ Healthcare, MSD, and Eli Lilly, has acted in a consultancy/advisory role for CJ Healthcare, DEA HWA Pharmaceutical and Eli Lilly, has received research funding from Alpha Biopharma, ASLAN Pharmaceuticals, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Chong Kun Dang Pharmaceutical, CJ Healthcare, Five Prime Therapeutics, Hanmi, Eli Lilly, Merck, Novotech, Ono Pharmaceutical, Pfizer, Sanofi and Yuhan, has provided expert testimony for CJ Healthcare, and has received travel/accommodation/expenses from Boehringer Ingelheim. OakPil Han, Young Su Noh and Ka Young Hong are employees of Hanmi Pharmaceutical Co., Ltd. Keunchil Park has acted in consultancy/advisory roles for Amgen, Astellas, AbbVie, AstraZeneca, Boehringer Ingelheim, BluePrint, BMS, Clovis, Eli Lilly, GSK, Hanmi, KHK, Merck, MSD, Novartis, Ono Pharm and Roche, and has received research funding from AstraZeneca. The remaining authors have no conflicts of interest to disclose.
This study was funded by Hanmi Pharmaceutical Co., Ltd . We thank the patients, their families, and the investigators for their participation in this trial. We also thank the members of the study team (Hanmi Pharmaceutical Co., Ltd). Professional medical writing assistance was provided by David Murdoch and David P. Figgitt PhD, ISMPP CMPP™, Content Ed Net, with funding from Hanmi Pharmaceutical Co., Ltd.
© 2019 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine
- Cancer Research