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Phase 1a study of the CDK4/6 inhibitor, FCN-437c, in Chinese patients with HR + /HER2- advanced breast cancer.
Zhang, Jian; Wang, Xiaojia; Wang, Xian; Hui, Aimin; Wu, Zhuli; Tian, Ling; Xu, Changjiang; Yang, Yuchen; Zhang, Wenjing; Hu, Xichun.
Affiliation
  • Zhang J; Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
  • Wang X; Department of Breast Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 Banshan East Street, Gongshu District, Hangzhou, 310022, China.
  • Wang X; Department of Medical Oncology, Sir Run Run Shaw Hospital, 3 Qingchun East Road, Hangzhou, 310016, China.
  • Hui A; Fosun Pharma USA Inc, 91 Hartwell Ave Suite 305, Lexington, MA, 02421, USA.
  • Wu Z; Beijing Fosun Pharmaceutical Research and Development Co., Ltd, 1289 Yishan Road, Shanghai, 200233, China.
  • Tian L; Avanc Pharmaceutical Co., Ltd, 55 Songshan Street, Jinzhou, 121013, China.
  • Xu C; Beijing Fosun Pharmaceutical Research and Development Co., Ltd, 1289 Yishan Road, Shanghai, 200233, China.
  • Yang Y; Beijing Fosun Pharmaceutical Research and Development Co., Ltd, 1289 Yishan Road, Shanghai, 200233, China.
  • Zhang W; Beijing Fosun Pharmaceutical Research and Development Co., Ltd, 1289 Yishan Road, Shanghai, 200233, China.
  • Hu X; Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China. xchu2009@hotmail.com.
Invest New Drugs ; 39(6): 1549-1558, 2021 12.
Article in En | MEDLINE | ID: mdl-34109484
Purpose This phase 1a, first-in-human study assessed the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and antitumor activity of FCN-437c, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Methods The study enrolled female patients with HR + /HER2- advanced breast cancer (BC) who failed standard of care therapy. A 3 + 3 dose-escalation design was utilized with a starting dose of 50 mg daily for 3 weeks on and 1 week off treatment in 28-day cycles. Patients received escalating doses of FCN-437c monotherapy (50, 100, 200, 300, and 450 mg). Results Seventeen patients received FCN-437c 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 300 mg (n = 6), and 450 mg (n = 2). Two patients who received the 450-mg dose experienced dose-limiting toxicities (DLTs; grade 4 thrombocytopenia and neutropenia); no DLT was observed at any other dose level. Frequently reported treatment-emergent adverse events (TEAEs) of any grade were hematological: leukopenia (94.1%), neutropenia (88.2%), anemia (64.7%), and thrombocytopenia (47.1%). Grade 3-4 TEAEs included neutropenia (64.7%) and leukopenia (47.1%). Exposure of FCN-437c increased almost proportionally to doses ranging from 50 to 200 mg. At doses from 200 to 450 mg, there appeared to be a trend of saturation. The MTD was determined to be 300 mg. Of 15 patients with measurable disease, nine (60.0%) patients experienced stable disease; no complete or partial responses were observed. Conclusions These results established an acceptable safety profile for FCN-437c in patients with advanced BC, and there were no unexpected signals relative to other CDK4/6 inhibitors. (NCT04488107; July 13, 2020).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Protein Kinase Inhibitors / Cyclin-Dependent Kinase 4 / Antineoplastic Agents Type of study: Clinical_trials / Prognostic_studies Limits: Adult / Aged / Female / Humans / Middle aged Country/Region as subject: Asia Language: En Journal: Invest New Drugs Year: 2021 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Protein Kinase Inhibitors / Cyclin-Dependent Kinase 4 / Antineoplastic Agents Type of study: Clinical_trials / Prognostic_studies Limits: Adult / Aged / Female / Humans / Middle aged Country/Region as subject: Asia Language: En Journal: Invest New Drugs Year: 2021 Document type: Article