A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer
| Autor: | Yeul Hong Kim, Do Youn Oh, Daisuke Sakai, Se Hoon Park, Toshihiko Doi, Ayuko Yamamura, Akihito Tsuji, Yoon-Koo Kang, Sameera R. Wijayawardana, Xuejing Wang, Yoshito Komatsu, Shigenori Kadowaki, Kazunori Uenaka, Hyun Cheol Chung, Volker Wacheck |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Target lesion Cancer Research medicine.medical_specialty Stomach neoplasms Phases of clinical research Pharmacology Antibodies Monoclonal Humanized Toxicology Gastroenterology Disease-Free Survival 03 medical and health sciences 0302 clinical medicine Asian People Pharmacokinetics Internal medicine Antibodies Bispecific medicine Clinical endpoint Humans Pharmacology (medical) Adverse effect Survival rate Aged MET protein human business.industry Middle Aged medicine.disease Phase II LY2875358 Clinical trial 030104 developmental biology Oncology 030220 oncology & carcinogenesis Original Article Female Hyponatremia business |
| Zdroj: | Cancer Chemotherapy and Pharmacology |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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