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

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3 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)1-11
Number of pages11
JournalCancer Chemotherapy and Pharmacology
DOIs
Publication statusAccepted/In press - 2017 Oct 25

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Keywords

  • Antibodies, monoclonal, humanized
  • Clinical trial
  • LY2875358
  • MET protein, human
  • Phase II
  • Stomach neoplasms

ASJC Scopus subject areas

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

Cite this

Sakai, D., Chung, H. C., Oh, D. Y., Park, S. H., Kadowaki, S., Kim, Y. H., Tsuji, A., Komatsu, Y., Kang, Y. K., Uenaka, K., Wijayawardana, S. R., Wacheck, V., Wang, X., Yamamura, A., & Doi, T. (Accepted/In press). A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer. Cancer Chemotherapy and Pharmacology, 1-11. https://doi.org/10.1007/s00280-017-3445-z