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Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer

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Abstract

Purpose

Transforming growth factor-beta inhibitors may enhance the antitumor activity of gemcitabine with acceptable safety and tolerability. This open-label, multicenter, non-randomized phase 1b study assessed the safety/tolerability, pharmacokinetics, and tumor response of galunisertib plus gemcitabine in Japanese patients with advanced or metastatic pancreatic cancer.

Methods

During each 28-day cycle, galunisertib 150 mg was administered orally twice daily (300 mg/day) for 14 days, followed by 14 days of rest. Gemcitabine 1000 mg/m2 was intravenously given on Days 8, 15, and 22. Safety was assessed by the incidence of dose-limiting toxicities (DLTs) in the first cycle and treatment-emergent adverse events (TEAEs). Efficacy was assessed by antitumor activity and changes in carbohydrate antigen 19-9 (CA19-9).

Results

No DLTs were reported. All 7 enrolled patients had ≥1 TEAE, of which the most common included anorexia, decreased neutrophil count, and decreased white blood cell count. Grade ≥3 TEAEs were observed in 6 patients; 4 patients had Grade ≥3 TEAEs (decreased neutrophil, white blood cell, and lymphocyte count; hypophosphatemia) considered possibly related to study drug(s). The pharmacokinetic profile of galunisertib in combination with gemcitabine was similar to that previously observed for galunisertib alone. The clinical response [complete response (CR), partial response (PR), or stable disease] rate was 42.9%, and the median progression-free survival was 64 days; no CR/PR were achieved.

Conclusion

Galunisertib plus gemcitabine had an acceptable safety/tolerability profile with evidence of efficacy in Japanese patients with advanced or metastatic pancreatic cancer.

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Acknowledgements

The authors would like to thank all study participants and their families. We also wish to thank the study team members at the study centers, Eli Lilly and Company, and the CROs.

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Authors and Affiliations

  1. National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Masafumi Ikeda & Hideaki Takahashi

  2. National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Shunsuke Kondo & Hideki Ueno

  3. 6820 Wisconsin Avenue, Bethesda, MD, 20815, USA

    Michael Mauritius Fabio Lahn

  4. Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA

    Ken Ogasawara

  5. Eli Lilly and Company, Bridgewater, NJ, USA

    Karim A. Benhadji

  6. Eli Lilly Japan K.K., 7-1-5 Isogamidori, Chuo-Ku, Kobe, 651-0086, Japan

    Hisaki Fujii

Authors
  1. Masafumi Ikeda
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  2. Hideaki Takahashi
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  3. Shunsuke Kondo
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  4. Michael Mauritius Fabio Lahn
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  5. Ken Ogasawara
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  7. Hisaki Fujii
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Contributions

All authors participated in the interpretation of study results, and in the drafting, critical revision, and approval of the final version of the manuscript. MI, ML, KO, and HU were involved in the study design and data analyses. MI and HU were involved in data collection. MI, HT, SK, and HU were investigators in the study, and KO conducted the pharmacokinetic analysis. KB was involved in the analysis and interpretation of data.

Corresponding author

Correspondence to Masafumi Ikeda.

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Funding

This study was sponsored by Eli Lilly Japan, manufacturer/licensee of galunisertib (LY2157299 monohydrate, Grant Number H9H-JE-JBAO). Medical writing assistance was provided by Mark Snape, MB BS, CMPP and Hiroko Ebina, BPharm, Ph, MBA 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). Eli Lilly Japan was involved in the study design, data collection, data analysis, and preparation of the manuscript.

Conflict of interest

KB/HF and ML/KO are current and former employees of Eli Lilly and Company, respectively. ML, KB, and HF own shares in Eli Lilly and Company. MI has received research funding from Taiho and Eli Lilly and Company, SK has received research funding from Eli Lilly and Company, Pfizer, Aslan Pharmaceuticals, AstraZeneca and Bayer, and HU has received research funding from Taiho and Eli Lilly and Company, and has been involved in a speakers’ bureau with Taiho. HT has no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Ikeda, M., Takahashi, H., Kondo, S. et al. Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer. Cancer Chemother Pharmacol 79, 1169–1177 (2017). https://doi.org/10.1007/s00280-017-3313-x

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  • DOI: https://doi.org/10.1007/s00280-017-3313-x

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