Safety, tolerability, and anti-tumor activity of olmutinib in non-small cell lung cancer with T790M mutation: A single arm, open label, phase 1/2 trial

Dong Wan Kim, Dae Ho Lee, Ji Youn Han, Jongseok Lee, Byoung Chul Cho, Jin Hyoung Kang, Ki Hyeong Lee, Eun Kyung Cho, Jin Soo Kim, Young Joo Min, Jae Yong Cho, Ho Jung An, Hoon Gu Kim, Kyung Hee Lee, Bong Seog Kim, In Jin Jang, Seonghae Yoon, Oak Pil Han, Young Su Noh, Ka Young HongKeunchil Park

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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.

Original languageEnglish
Pages (from-to)66-72
Number of pages7
JournalLung Cancer
Volume135
DOIs
Publication statusPublished - 2019 Sep

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Kim, D. W., Lee, D. H., Han, J. Y., Lee, J., Cho, B. C., Kang, J. H., Lee, K. H., Cho, E. K., Kim, J. S., Min, Y. J., Cho, J. Y., An, H. J., Kim, H. G., Lee, K. H., Kim, B. S., Jang, I. J., Yoon, S., Han, O. P., Noh, Y. S., ... Park, K. (2019). Safety, tolerability, and anti-tumor activity of olmutinib in non-small cell lung cancer with T790M mutation: A single arm, open label, phase 1/2 trial. Lung Cancer, 135, 66-72. https://doi.org/10.1016/j.lungcan.2019.07.007