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 language | English |
|---|---|
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Cancer Chemotherapy and Pharmacology |
| DOIs | |
| Publication status | Accepted/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
A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer. / 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.
In: Cancer Chemotherapy and Pharmacology, 25.10.2017, p. 1-11.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer
AU - Sakai, Daisuke
AU - Chung, Hyun Cheol
AU - Oh, Do Youn
AU - Park, Se Hoon
AU - Kadowaki, Shigenori
AU - Kim, Yeul Hong
AU - Tsuji, Akihito
AU - Komatsu, Yoshito
AU - Kang, Yoon Koo
AU - Uenaka, Kazunori
AU - Wijayawardana, Sameera R.
AU - Wacheck, Volker
AU - Wang, Xuejing
AU - Yamamura, Ayuko
AU - Doi, Toshihiko
PY - 2017/10/25
Y1 - 2017/10/25
N2 - 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.
AB - 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.
KW - Antibodies, monoclonal, humanized
KW - Clinical trial
KW - LY2875358
KW - MET protein, human
KW - Phase II
KW - Stomach neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85032217585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032217585&partnerID=8YFLogxK
U2 - 10.1007/s00280-017-3445-z
DO - 10.1007/s00280-017-3445-z
M3 - Article
SP - 1
EP - 11
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
ER -