A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer

Daisuke Sakai, Hyun Cheol Chung, Do Youn Oh, Se Hoon Park, Shigenori Kadowaki, Yeul Hong Kim, Akihito Tsuji, Yoshito Komatsu, Yoon Koo Kang, Kazunori Uenaka, Sameera R. Wijayawardana, Volker Wacheck, Xuejing Wang, Ayuko Yamamura, Toshihiko Doi

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Purpose: Mesenchymal–epithelial transition factor (MET) is expressed in gastric cancer and associated with poor clinical outcomes. We assessed activity, safety, and pharmacokinetics of emibetuzumab, a bivalent monoclonal anti-MET antibody that blocks ligand-dependent and ligand-independent MET signaling. Methods: This non-randomized, single-arm, Phase 2 study enrolled Asian patients with MET diagnostic positive advanced gastric adenocarcinoma. Emibetuzumab (2000 mg, intravenous) was given on days 1 and 15 (28-day cycle). The primary endpoint was 8-week progression-free survival rate. Secondary objectives included safety, pharmacokinetics, overall survival, and change in tumor size. Results: Tumors from 65 patients were immunohistochemically screened to enroll 15 MET diagnostic positive patients (23% positivity; 8 Japanese, 7 Korean; 10 male). Eight-week progression-free survival rate was 0.47 (70% CI, 0.33–0.59). Disease control rate was 40% (target lesion decreases, three patients; no complete/partial responses according to RECIST). Median overall survival was 17.1 weeks (95% CI, 6.3–not achievable). No serious emibetuzumab-related adverse events or new safety signals emerged. Grade ≥ 3 possibly drug-related adverse events were hyperkalemia, hyponatremia, and hyperuricemia (one each). Emibetuzumab’s pharmacokinetics profile was similar to that observed previously. MET expression and clinical outcomes were not obviously associated. Conclusion: Emibetuzumab was well tolerated with limited single-agent activity in advanced gastric adenocarcinoma.

Original languageEnglish
Pages (from-to)1197-1207
Number of pages11
JournalCancer Chemotherapy and Pharmacology
Volume80
Issue number6
DOIs
Publication statusPublished - 2017 Dec 1

Bibliographical note

Funding Information:
Conflict of interest HCC has received research funding from Eli Lilly and Company, GSK, and MSD, has participated in consultancies and advisory panels for Taiho Pharmaceutical, Celltrion, MSD, Eli Lilly and Company, Quintiles, BMS, and Atheneum Partners, and has participated in speakers’ bureaus for Eli Lilly and Company and Merck Serono. D-YO has received research funding from Eli Lilly and Company. SK has participated in speakers’ bureaus for Eli Lilly Japan. YHK and TD have received research funding from Eli Lilly and Company, and participated in consultancies and advisory panels for Eli Lilly and Company. AT has participated in speakers’ bureaus for Taiho Pharmaceutical, Takeda, Chugai, and Merck. YK has received research funding from Eli Lilly, MSD, Merck Serono, Chugai, Yakult, Bayer, Ono, Taiho Pharmaceutical, Daiichi-Sankyo, Dainippon, Am-gen, Takeda, and BMS, and has participated in speakers’ bureaus for Eli Lilly, Merck Serono, Chugai, Yakult, Bayer, Taiho Pharmaceutical, Daiichi-Sankyo, Takeda, and BMS. Y-KK has participated in consultancies and advisory panels for Eli Lilly and Company, Novartis, Ono, BMS, Blueprint Medicines, Roche, Taiho Pharmaceutical, and Dae-hwa Pharmaceutical. SRW, VW, and XAW are Eli Lilly and Company employees and shareholders. AY and KU are employees of Eli Lilly Japan K.K. DS has no conflicts of interest to declare.

Funding Information:
Funding support This study was sponsored by Eli Lilly and Company. Medical writing assistance was provided by Suzanne Habjan, PhD and Justine Southby, PhD, CMPP of ProScribe—Envision Pharma Group, and was funded by Eli Lilly and Company. ProScribe’s services complied with international guidelines for Good Publication Practice (GPP3).

Publisher Copyright:
© 2017, The Author(s).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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