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A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors

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Abstract

Purpose

Combination treatment using lenvatinib (a multikinase inhibitor) plus pembrolizumab (a programmed death-1 immune checkpoint inhibitor) has shown efficacy in the treatment of endometrial and renal cell cancers. This phase 1b study investigated the tolerability and safety of lenvatinib plus pembrolizumab in Japanese patients with metastatic selected solid tumors.

Methods

Patients received a starting dose of 20 mg oral lenvatinib per day plus 200 mg intravenous pembrolizumab every 3 weeks in 21-day cycles. Dose-limiting toxicities were evaluated during the first cycle. Tumor assessments were performed by investigators based on modified RECIST v1.1. Pharmacokinetic parameters and serum biomarkers were assessed.

Results

Among enrolled patients (N = 6), 3 had non-small cell lung cancer, and 3 had urothelial cancer. No patients experienced a dose-limiting toxicity. All patients experienced at least 1 treatment-related treatment-emergent adverse event. The objective response rate was 33.3% (95% confidence interval 4.3–77.7); both responses (1 complete, 1 partial) were observed in patients with urothelial cancer. Pharmacokinetics were consistent with previous studies. Serum angiopoietin-2 levels tended to decrease, and serum fibroblast growth factor-23 levels tended to increase from baseline to Cycle 2 Day 1.

Conclusions

This study supports the tolerability of 20 mg lenvatinib/day plus 200 mg pembrolizumab every 3 weeks in Japanese patients, consistent with the results from a global study of lenvatinib plus pembrolizumab combination therapy in patients with selected solid tumors. Favorable antitumor activity was observed and there were no new safety signals identified.

Trial registration

Clinical Trials.gov number: NCT03006887.

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Fig. 1

Data availability

The data will not be available for sharing at this time because the data are commercially confidential. However, Eisai will consider written requests to share the data on a case-by-case basis.

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Acknowledgements

Medical writing support was provided by Heather A. Mitchell, PhD, Oxford PharmaGenesis Inc., Newtown, PA, USA.

Funding

This study was funded by Eisai Inc., Nutley, NJ, USA. Study support was also provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Medical writing support was funded by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Author information

Authors and Affiliations

  1. Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan

    Shigehisa Kitano, Yutaka Fujiwara, Toshio Shimizu, Satoru Iwasa, Kan Yonemori, Shunsuke Kondo, Akihiko Shimomura, Takafumi Koyama, Takahiro Ebata & Noboru Yamamoto

  2. Department of Advanced Medical Development, The Cancer Institute Hospital of JFCR, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Shigehisa Kitano

  3. Department of Thoracic Oncology, Aichi Cancer Center, Nagoya, Japan

    Yutaka Fujiwara

  4. Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan

    Akihiko Shimomura

  5. Clinical Data Science Department, Eisai Co., Ltd, Tokyo, Japan

    Hiroki Ikezawa

  6. Clinical Pharmacology Science Department, Eisai Co., Ltd, Tokyo, Japan

    Nozomi Hayata

  7. Tsukuba Research Laboratories, Eisai Co., Ltd, Ibaraki, Japan

    Yukinori Minoshima

  8. Japan and Asia Clinical Development Department, Eisai Co., Ltd, Tokyo, Japan

    Takuma Miura & Tomoki Kubota

Authors
  1. Shigehisa Kitano
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  2. Yutaka Fujiwara
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  3. Toshio Shimizu
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  4. Satoru Iwasa
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  5. Kan Yonemori
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  6. Shunsuke Kondo
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  7. Akihiko Shimomura
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  8. Takafumi Koyama
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  9. Takahiro Ebata
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  10. Hiroki Ikezawa
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  11. Nozomi Hayata
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  12. Yukinori Minoshima
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  13. Takuma Miura
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  15. Noboru Yamamoto
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Contributions

Conceptualization: SK, HI, NH, YM, Miura, TK, NY. Methodology: HI, NH, YM, TM, TK. Data acquisition: SK, YF, TS, SI, KY, SK, AS, TK, TE, NY. Data analysis: NH, HI, YM. Data interpretation: all authors. Writing (original draft, review, editing): all authors. Approval of final manuscript: all authors.

Corresponding author

Correspondence to Shigehisa Kitano.

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Conflict of interest

Shigehisa Kitano reports remuneration from ImmuniT Research Inc; honoraria from Ono Pharmaceutical, Bristol Myers Squibb, Astra Zeneca, Chugai, MSD, and Pfizer; and research funds from Eisai, REGENERON, Boehringer Ingelheim, Astellas Pharma, Gilead Sciences, Daiichi Sankyo, Takara Bio, Ono Pharmaceutical, PACT Pharma, Chugai, and MSD. Yutaka Fujiwara reports research funding from Bristol-Myers Squibb and Chugai; and honoraria from Astra Zeneca, Chugai, Daiichi Sankyo, Novartis, ONO Pharmaceutical, Otsuka Pharmaceutical, and Pfizer, outside the submitted work. Toshio Shimizu reports research funds from Novartis, Eli Lilly, Daiichi-Sankyo, Bristol Myers Squibb, AbbVie, Eisai, AstraZeneca, Takeda Oncology, Incyte, Chordia Therapeutics, 3D-Medicine, Symbio Pharmaceuticals, PharmaMar, Pfizer, Five Prime and Astellas Pharma. Satoru Iwasa has nothing to disclose. Kan Yonemori reports lecture fees from Eisai, Taiho, Pfizer, Eli Lilly, AstraZeneca, Takeda, Fuji Film, and Chugai; is an advisor for Takeda, Eisai, Novartis, Chugai, Ono, and AstraZeneca; has received grants for clinical trials from MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, and Nihon Kayaku. Shunsuke Kondo has nothing to disclose. Akihiko Shimomura reports honoraria from Chugai Pharmaceutical and Eli-Lilly Japan, and research funds from Chugai Pharmaceutical, AstraZeneca, Daiichi Sankyo, and Taiho Pharmaceutical. Takafumi Koyama reports honoraria from Sysmex. Takahiro Ebata has nothing to disclose. Hiroki Ikezawa is an employee of Eisai Co., Ltd. Nozomi Hayata is an employee of Eisai Co., Ltd. Yukinori Minoshima is an employee of Eisai Co., Ltd. Tomoki Kubota is an employee of Eisai Co., Ltd. Takuma Miura is an employee of Eisai Co., Ltd. Noboru Yamamoto reports honoraria from Chugai, Pfizer and Sysmex; and research funds from Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO, Janssen Pharma, MSD, MERCK, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka, Carna Biosciences, and Genmab.

Ethical approval

The study protocol was approved by relevant institutional review boards and conducted in accordance with the principles of the World Medical Association Declaration of Helsinki and Japan’s Good Clinical Practice. The protocol, informed consent form, and appropriate related documents were reviewed by the Institutional Review Board of National Cancer Center, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Consent to participate

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

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Not applicable.

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Kitano, S., Fujiwara, Y., Shimizu, T. et al. A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 90, 523–529 (2022). https://doi.org/10.1007/s00280-022-04480-w

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  • DOI: https://doi.org/10.1007/s00280-022-04480-w

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