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
Cancer chemotherapy and pharmacology
2017Oct ; 7 ( 10 ) :.
PMID : 29071414
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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 -
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.
Antibodies, monoclonal, humanized; Clinical trial; Phase II; LY2875358; MET protein, human; Stomach neoplasms
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