Dong-Wan Kim1, Dae Ho Lee2, Ji-Youn Han3, Jongseok Lee4, Byoung Chul Cho5, Jin Hyoung Kang6, Ki Hyeong Lee7, Eun Kyung Cho8, Jin-Soo Kim9, Young Joo Min10, Jae Yong Cho11, Ho Jung An12, Hoon-Gu Kim13, Kyung Hee Lee14, Bong-Seog Kim15, In-Jin Jang16, Seonghae Yoon17, OakPil Han18, Young Su Noh19, Ka Young Hong18, Keunchil Park20. 1. Seoul National University Hospital, Seoul, South Korea. Electronic address: kimdw@snu.ac.kr. 2. University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. 3. Center for Lung Cancer, National Cancer Center, Goyang, South Korea. 4. Seoul National University Bundang Hospital, Seoul, South Korea. 5. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. 6. Catholic University of Korea, Seoul St Mary's Hospital, Seoul, South Korea. 7. Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea. 8. Gil Medical Center, Gachon University School of Medicine, Incheon, South Korea. 9. Seoul National University Boramae Medical Center, Seoul, South Korea. 10. University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea. 11. Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea. 12. Catholic University of Korea, St Vincent's Hospital, Seoul, South Korea. 13. Gyeongsang National University College of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea. 14. Yeungnam University Medical Center, Daegu, South Korea. 15. Veterans Health Service Medical Center, Seoul, South Korea. 16. Seoul National University and Hospital, Seoul, South Korea. 17. Seoul National University Bundang Hospital, Seoul, South Korea; Seoul National University and Hospital, Seoul, South Korea. 18. Hanmi Pharmaceutical Co., Ltd., Seoul, South Korea. 19. Hanmi Pharmaceutical Co., Ltd., Seoul, South Korea; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, South Korea. 20. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Abstract
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.
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 NSCLCpatients who have failed ≥ 1 previous line of EGFR-TKI therapy.