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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)1-11
Number of pages11
JournalCancer Chemotherapy and Pharmacology
DOIs
Publication statusAccepted/In press - 2017 Oct 25

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Pharmacokinetics
Stomach Neoplasms
Labels
Tumors
Safety
Disease control
Ligands
Disease-Free Survival
Stomach
Adenocarcinoma
Survival Rate
Hyperuricemia
Hyperkalemia
Survival
Hyponatremia
Drug-Related Side Effects and Adverse Reactions
Neoplasms
Antibodies
Pharmaceutical Preparations

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 journalArticle

Sakai, D, Chung, HC, Oh, DY, Park, SH, Kadowaki, S, Kim, YH, Tsuji, A, Komatsu, Y, Kang, YK, Uenaka, K, Wijayawardana, SR, Wacheck, V, Wang, X, Yamamura, A & Doi, T 2017, 'A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer', Cancer Chemotherapy and Pharmacology, pp. 1-11. https://doi.org/10.1007/s00280-017-3445-z
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. / A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer. In: Cancer Chemotherapy and Pharmacology. 2017 ; pp. 1-11.
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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.",
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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.

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KW - Stomach neoplasms

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