Clinical activity of ASP 8273 in Asian patients with non‐small‐cell lung cancer with EGFR activating and T790M mutations
Open accessAbstract
Epidermal growth factor receptor (EGFR)‐activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non‐small‐cell lung cancer (NSCLC). ASP 8273 is a highly specific, irreversible, once‐daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP 8273 dose‐escalation/dose‐expansion study (NCT 02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP 8273 doses (25‐600 mg) to assess safety/tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP 2D) by the Bayesian Continual Reassessment Method. In phase II, adult patients with T790M‐positive NSCLC in Japan, Korea, and Taiwan received ASP 8273 at RP 2D to further assess safety/tolerability and determine antitumor activity, which was evaluated according to Simon's two‐stage design (threshold response = 30%, expected response = 50%, α = 0.05, β = 0.1). Overall, 121 (n = 45 [33W/12M] phase I, n = 76 [48W/28M]) phase 2) patients received ≥1 dose of ASP 8273. In phase I, RP 2D and MTD were established as 300 and 400 mg, respectively. As 27 of the 63 patients treated with ASP 8273 300 mg achieved a clinical response, ASP 8273 was determined to have antitumor activity. The overall response rate at week 24 in all patients was 42% (n = 32/76; 95% confidence interval, 30.9‐54.0). Median duration of progression‐free survival was 8.1 months (95% confidence interval, 5.6, upper bound not reached). The most commonly reported treatment‐related adverse event in phase II was diarrhea (57%, n = 43/76). ASP 8273 300 mg was generally well tolerated and showed antitumor activity in Asian patients with both EGFR‐activating and T790M mutations.
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
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- Authors
- Murakami, H., Nokihara, H., Hayashi, H., Seto, T., Park, K., Azuma, K., Tsai, C., Yang, J. C., Nishio, M., Kim, S., Kiura, K., Inoue, A., Takeda, K., Kang, J., Nakagawa, T., Takeda, K., Akazawa, R., Kaneko, Y., Shimazaki, M., Morita, S., Fukuoka, M., & Nakagawa, K.
- Affiliations
- Shizuoka Cancer Center (JP)
- Tokushima University Hospital (JP)
- Kindai University Hospital (JP)
- National Hospital Organization Kyushu Cancer Center (JP)
- Samsung Medical Center (KR)
- Kurume University Hospital (JP)
- Taipei Veterans General Hospital (TW)
- National Taiwan University Hospital (TW)
- The Cancer Institute Hospital (JP)
- Asan Medical Center (KR)
- Okayama University Hospital (JP)
- Tohoku University Hospital (JP)
- Astellas Pharma (Japan) (JP)
- The Catholic University of Korea Seoul St. Mary's Hospital (KR)
- Kyoto University (JP)
- Izumi City General Hospital (JP)
- Corresponding author
- Murakami, Haruyasu
- ORCID
- Murakami, Haruyasu
- Nokihara, Hiroshi
- Hayashi, Hidetoshi
- Seto, Takashi
- Park, Keunchil
- Azuma, Koichi
- Tsai, Chun‐Ming
- Yang, James Chih‐Hsin
- Nishio, Makoto
- Kim, Sang‐We
- Kiura, Katsuyuki
- Inoue, Akira
- Takeda, Koji
- Kang, Jin‐Hyoung
- Nakagawa, Tomoki
- Takeda, Kentaro
- Kaneko, Yuichiro
- Shimazaki, Masashi
- Morita, Satoshi
- Nakagawa, Kazuhiko
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2018-08-09
- Volume
- 109
- Issue
- 9
- Pages
- 2852-2862
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC6125469
- OpenAlex
- W2810244791
- Cited by
- 17
- References
- 10
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 4
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Science (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Astellas Pharma
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- non-small cell lung cancer, EGFR activating mutations, T790M mutation, EGFR tyrosine kinase inhibitors, irreversible EGFR inhibitors, Asian patients, dose escalation, maximum tolerated dose, anticancer activity, diarrhea adverse event, progression-free survival, EGFR tyrosine kinase inhibitor resistance, Japanese patients, Korean patients, Taiwanese patients, Simon two-stage design
- MeSH terms
- Adult, Aged, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Piperazines, Piperidines, Pyrazines, Pyrrolidines, Protein Kinase Inhibitors, ErbB Receptors
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