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 Hong & 1 others Keunchil Park

Research output: Contribution to journalArticleResearchpeer-review

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
StatePublished - 1 Sep 2019

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Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Safety
Mutation
Neoplasms
Protein-Tyrosine Kinases
Pharmacokinetics
Therapeutics
Pruritus
Exanthema
Nausea
Disease-Free Survival
Diarrhea
Survival

Keywords

  • Clinical trial
  • EGFR-TKI
  • Non-Small call lung cancer
  • Olmutinib
  • T790M mutation

Cite this

Kim, Dong-Wan ; Lee, Dae Ho ; Han, Ji Youn ; Lee, Jongseok ; Cho, Byoung Chul ; Kang, Jin Hyoung ; Lee, Ki Hyeong ; Cho, Eun Kyung ; Kim, Jin Soo ; Min, Young Joo ; Cho, Jae Yong ; An, Ho Jung ; Kim, Hoon Gu ; Lee, Kyung Hee ; Kim, Bong Seog ; Jang, In Jin ; Yoon, Seonghae ; Han, Oak Pil ; Noh, Young Su ; Hong, Ka Young ; Park, Keunchil. / 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. In: Lung Cancer. 2019 ; Vol. 135. pp. 66-72.
@article{8adc3a9fc0214ec0a24ab84dea6f9e56,
title = "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",
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.",
keywords = "Clinical trial, EGFR-TKI, Non-Small call lung cancer, Olmutinib, T790M mutation",
author = "Dong-Wan Kim and Lee, {Dae Ho} and Han, {Ji Youn} and Jongseok Lee and Cho, {Byoung Chul} and Kang, {Jin Hyoung} and Lee, {Ki Hyeong} and Cho, {Eun Kyung} and Kim, {Jin Soo} and Min, {Young Joo} and Cho, {Jae Yong} and An, {Ho Jung} and Kim, {Hoon Gu} and Lee, {Kyung Hee} and Kim, {Bong Seog} and Jang, {In Jin} and Seonghae Yoon and Han, {Oak Pil} and Noh, {Young Su} and Hong, {Ka Young} and Keunchil Park",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.lungcan.2019.07.007",
language = "English",
volume = "135",
pages = "66--72",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

Kim, D-W, Lee, DH, Han, JY, Lee, J, Cho, BC, Kang, JH, Lee, KH, Cho, EK, Kim, JS, Min, YJ, Cho, JY, An, HJ, Kim, HG, Lee, KH, Kim, BS, Jang, IJ, Yoon, S, Han, OP, Noh, YS, Hong, KY & 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, vol. 135, pp. 66-72. https://doi.org/10.1016/j.lungcan.2019.07.007

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

In: Lung Cancer, Vol. 135, 01.09.2019, p. 66-72.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Safety, tolerability, and anti-tumor activity of olmutinib in non-small cell lung cancer with T790M mutation

T2 - A single arm, open label, phase 1/2 trial

AU - Kim, Dong-Wan

AU - Lee, Dae Ho

AU - Han, Ji Youn

AU - Lee, Jongseok

AU - Cho, Byoung Chul

AU - Kang, Jin Hyoung

AU - Lee, Ki Hyeong

AU - Cho, Eun Kyung

AU - Kim, Jin Soo

AU - Min, Young Joo

AU - Cho, Jae Yong

AU - An, Ho Jung

AU - Kim, Hoon Gu

AU - Lee, Kyung Hee

AU - Kim, Bong Seog

AU - Jang, In Jin

AU - Yoon, Seonghae

AU - Han, Oak Pil

AU - Noh, Young Su

AU - Hong, Ka Young

AU - Park, Keunchil

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

KW - Clinical trial

KW - EGFR-TKI

KW - Non-Small call lung cancer

KW - Olmutinib

KW - T790M mutation

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U2 - 10.1016/j.lungcan.2019.07.007

DO - 10.1016/j.lungcan.2019.07.007

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EP - 72

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

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