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

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

来源：Cancer Chemotherapy and Pharmacology, 2017, 80(6): 1197-1207.

DOI：10.1007/s00280-017-3445-z

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

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.

• 出版日期2017-12