1. Academic Validation
  2. A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors

A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors

  • Invest New Drugs. 2020 Feb;38(1):99-110. doi: 10.1007/s10637-019-00745-z.
Jih-Hsiang Lee 1 Tom Wei-Wu Chen 2 Chih-Hung Hsu 2 3 Yu-Hsin Yen 2 James Chih-Hsin Yang 2 3 Ann-Lii Cheng 2 3 Shun-Ichi Sasaki 4 LiYin Lillian Chiu 5 Masahiro Sugihara 4 Tomoko Ishizuka 4 Toshihiro Oguma 4 Naoyuki Tajima 4 Chia-Chi Lin 6 7
Affiliations

Affiliations

  • 1 National Taiwan University Hospital, Hsin-Chu Branch No. 25, Lane 442, Sec. 1, Jingguo Rd, Hsinchu City, 300, Taiwan.
  • 2 National Taiwan University Hospital, 7 Chung Shan S Rd, Taipei, 10002, Taiwan.
  • 3 Graduate Institute of Oncology, National Taiwan University College of Medicine, 7 Chung Shan S Rd, Taipei, 10002, Taiwan.
  • 4 Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
  • 5 Daiichi Sankyo Co., Ltd., 7F-1, No. 308, Sec. 2, Bade Rd, Zhongshan Dist., Taipei City, 104, Taiwan.
  • 6 National Taiwan University Hospital, 7 Chung Shan S Rd, Taipei, 10002, Taiwan. cclin1@ntu.edu.tw.
  • 7 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 7 Chung Shan S Rd, Taipei, 10002, Taiwan. cclin1@ntu.edu.tw.
Abstract

Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d. Primary objectives assessed pexidartinib safety and tolerability, and determined the recommended phase 2 dose; secondary objectives evaluated efficacy and pharmacokinetic profile. Results All 11 patients (6 males, 5 females; median age 64, range 23-82; cohort 1 n = 3; cohort 2 n = 8) experienced at least one treatment-emergent adverse event; 5 experienced at least one grade ≥ 3 adverse event, most commonly (18%) for each of the following: increased aspartate aminotransferase, blood Alkaline Phosphatase, gamma-glutamyl transferase, and anemia. Recommended phase 2 dose was 1000 mg/d for 2 weeks and 800 mg/d thereafter. Pexidartinib exposure, area under the plasma concentration-time curve from zero to 8 h (AUC0-8h), and maximum observed plasma concentration (Cmax) increased on days 1 and 15 with increasing pexidartinib doses, and time at Cmax (Tmax) was consistent throughout all doses. Pexidartinib exposure and plasma levels of Adiponectin and colony-stimulating factor 1 increased following multiple daily pexidartinib administrations. One patient (13%) with tenosynovial giant cell tumor showed objective tumor response. Conclusions This was the first study to evaluate pexidartinib in Asian patients with advanced solid tumors. Pexidartinib was safe and tolerable in this population at the recommended phase 2 dose previously determined for Western patients (funded by Daiichi Sankyo; clinicaltrials.gov number, NCT02734433).

Keywords

Pexidartinib; Pharmacokinetics; Safety; Solid tumors; Tenosynovial giant cell tumor.

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