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

Autor:	Sakai, Daisuke, Chung, Hyun, Oh, Do-Youn, Park, Se, Kadowaki, Shigenori, Kim, Yeul, Tsuji, Akihito, Komatsu, Yoshito, Kang, Yoon-Koo, Uenaka, Kazunori, Wijayawardana, Sameera, Wacheck, Volker, Wang, Xuejing, Yamamura, Ayuko, Doi, Toshihiko, Chung, Hyun Cheol, Park, Se Hoon, Kim, Yeul Hong, Wijayawardana, Sameera R
Předmět:	STOMACH cancer GASTRIC diseases EPITHELIAL cells PROGRESSION-free survival ADENOCARCINOMA THERAPEUTIC use of immunoglobulins THERAPEUTIC use of monoclonal antibodies ASIANS CLINICAL trials COMPARATIVE studies RESEARCH methodology MEDICAL cooperation PROGNOSIS RESEARCH STOMACH tumors EVALUATION research
Zdroj:	Cancer Chemotherapy & Pharmacology; Dec2017, Vol. 80 Issue 6, p1197-1207, 11p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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