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

doi:10.1007/s00280-017-3445-z

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

24 Citations (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 language	English
Pages (from-to)	1197-1207
Number of pages	11
Journal	Cancer Chemotherapy and Pharmacology
Volume	80
Issue number	6
DOIs	https://doi.org/10.1007/s00280-017-3445-z
Publication status	Published - 2017 Dec 1

Bibliographical note

Funding Information:
Conflict of interest HCC has received research funding from Eli Lilly and Company, GSK, and MSD, has participated in consultancies and advisory panels for Taiho Pharmaceutical, Celltrion, MSD, Eli Lilly and Company, Quintiles, BMS, and Atheneum Partners, and has participated in speakers’ bureaus for Eli Lilly and Company and Merck Serono. D-YO has received research funding from Eli Lilly and Company. SK has participated in speakers’ bureaus for Eli Lilly Japan. YHK and TD have received research funding from Eli Lilly and Company, and participated in consultancies and advisory panels for Eli Lilly and Company. AT has participated in speakers’ bureaus for Taiho Pharmaceutical, Takeda, Chugai, and Merck. YK has received research funding from Eli Lilly, MSD, Merck Serono, Chugai, Yakult, Bayer, Ono, Taiho Pharmaceutical, Daiichi-Sankyo, Dainippon, Am-gen, Takeda, and BMS, and has participated in speakers’ bureaus for Eli Lilly, Merck Serono, Chugai, Yakult, Bayer, Taiho Pharmaceutical, Daiichi-Sankyo, Takeda, and BMS. Y-KK has participated in consultancies and advisory panels for Eli Lilly and Company, Novartis, Ono, BMS, Blueprint Medicines, Roche, Taiho Pharmaceutical, and Dae-hwa Pharmaceutical. SRW, VW, and XAW are Eli Lilly and Company employees and shareholders. AY and KU are employees of Eli Lilly Japan K.K. DS has no conflicts of interest to declare.

Funding Information:
Funding support This study was sponsored by Eli Lilly and Company. Medical writing assistance was provided by Suzanne Habjan, PhD and Justine Southby, PhD, CMPP of ProScribe—Envision Pharma Group, and was funded by Eli Lilly and Company. ProScribe’s services complied with international guidelines for Good Publication Practice (GPP3).

Publisher Copyright:
© 2017, The Author(s).

All Science Journal Classification (ASJC) codes

Oncology
Toxicology
Pharmacology
Cancer Research
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00280-017-3445-z

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Sakai, D., Chung, H. C., Oh, D. Y., Park, S. H., Kadowaki, S., Kim, Y. H., Tsuji, A., Komatsu, Y., Kang, Y. K., Uenaka, K., Wijayawardana, S. R., 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, 80(6), 1197-1207. https://doi.org/10.1007/s00280-017-3445-z

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

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{\textquoteright}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.",

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

note = "Funding Information: Conflict of interest HCC has received research funding from Eli Lilly and Company, GSK, and MSD, has participated in consultancies and advisory panels for Taiho Pharmaceutical, Celltrion, MSD, Eli Lilly and Company, Quintiles, BMS, and Atheneum Partners, and has participated in speakers{\textquoteright} bureaus for Eli Lilly and Company and Merck Serono. D-YO has received research funding from Eli Lilly and Company. SK has participated in speakers{\textquoteright} bureaus for Eli Lilly Japan. YHK and TD have received research funding from Eli Lilly and Company, and participated in consultancies and advisory panels for Eli Lilly and Company. AT has participated in speakers{\textquoteright} bureaus for Taiho Pharmaceutical, Takeda, Chugai, and Merck. YK has received research funding from Eli Lilly, MSD, Merck Serono, Chugai, Yakult, Bayer, Ono, Taiho Pharmaceutical, Daiichi-Sankyo, Dainippon, Am-gen, Takeda, and BMS, and has participated in speakers{\textquoteright} bureaus for Eli Lilly, Merck Serono, Chugai, Yakult, Bayer, Taiho Pharmaceutical, Daiichi-Sankyo, Takeda, and BMS. Y-KK has participated in consultancies and advisory panels for Eli Lilly and Company, Novartis, Ono, BMS, Blueprint Medicines, Roche, Taiho Pharmaceutical, and Dae-hwa Pharmaceutical. SRW, VW, and XAW are Eli Lilly and Company employees and shareholders. AY and KU are employees of Eli Lilly Japan K.K. DS has no conflicts of interest to declare. Funding Information: Funding support This study was sponsored by Eli Lilly and Company. Medical writing assistance was provided by Suzanne Habjan, PhD and Justine Southby, PhD, CMPP of ProScribe—Envision Pharma Group, and was funded by Eli Lilly and Company. ProScribe{\textquoteright}s services complied with international guidelines for Good Publication Practice (GPP3). Publisher Copyright: {\textcopyright} 2017, The Author(s).",

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day = "1",

doi = "10.1007/s00280-017-3445-z",

language = "English",

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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, vol. 80, no. 6, pp. 1197-1207. https://doi.org/10.1007/s00280-017-3445-z

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

N1 - Funding Information: Conflict of interest HCC has received research funding from Eli Lilly and Company, GSK, and MSD, has participated in consultancies and advisory panels for Taiho Pharmaceutical, Celltrion, MSD, Eli Lilly and Company, Quintiles, BMS, and Atheneum Partners, and has participated in speakers’ bureaus for Eli Lilly and Company and Merck Serono. D-YO has received research funding from Eli Lilly and Company. SK has participated in speakers’ bureaus for Eli Lilly Japan. YHK and TD have received research funding from Eli Lilly and Company, and participated in consultancies and advisory panels for Eli Lilly and Company. AT has participated in speakers’ bureaus for Taiho Pharmaceutical, Takeda, Chugai, and Merck. YK has received research funding from Eli Lilly, MSD, Merck Serono, Chugai, Yakult, Bayer, Ono, Taiho Pharmaceutical, Daiichi-Sankyo, Dainippon, Am-gen, Takeda, and BMS, and has participated in speakers’ bureaus for Eli Lilly, Merck Serono, Chugai, Yakult, Bayer, Taiho Pharmaceutical, Daiichi-Sankyo, Takeda, and BMS. Y-KK has participated in consultancies and advisory panels for Eli Lilly and Company, Novartis, Ono, BMS, Blueprint Medicines, Roche, Taiho Pharmaceutical, and Dae-hwa Pharmaceutical. SRW, VW, and XAW are Eli Lilly and Company employees and shareholders. AY and KU are employees of Eli Lilly Japan K.K. DS has no conflicts of interest to declare. Funding Information: Funding support This study was sponsored by Eli Lilly and Company. Medical writing assistance was provided by Suzanne Habjan, PhD and Justine Southby, PhD, CMPP of ProScribe—Envision Pharma Group, and was funded by Eli Lilly and Company. ProScribe’s services complied with international guidelines for Good Publication Practice (GPP3). Publisher Copyright: © 2017, The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

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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JO - Cancer Chemotherapy and Pharmacology

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ER -

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

Abstract

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UN SDGs

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