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Umehara H, Maekawa Y, Koizumi F, et al. Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole. Ther Adv Med Oncol. 2018;10:1758835918786858doi: 10.1177/1758835918786858.
Umehara, H., Maekawa, Y., Koizumi, F., Shimizu, M., Ota, T., Fouad, T. M., Willey, J., Kaito, H., Shiraishi, N., Nakashima, D., Akinaga, S., & Ueno, N. T. (2018). Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole. Therapeutic advances in medical oncology, 101758835918786858. https://doi.org/10.1177/1758835918786858
Umehara, Hiroshi, et al. "Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole." Therapeutic advances in medical oncology vol. 10 (2018): 1758835918786858. doi: https://doi.org/10.1177/1758835918786858
Umehara H, Maekawa Y, Koizumi F, Shimizu M, Ota T, Fouad TM, Willey J, Kaito H, Shiraishi N, Nakashima D, Akinaga S, Ueno NT. Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole. Ther Adv Med Oncol. 2018 Jul 30;10:1758835918786858. doi: 10.1177/1758835918786858. eCollection 2018. PMID: 30083253; PMCID: PMC6066809.
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Ther Adv Med Oncol. 2018 Jul 30;10:1758835918786858. doi: 10.1177/1758835918786858. eCollection 2018.

Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole.

Therapeutic advances in medical oncology

Hiroshi Umehara, Yoshimi Maekawa, Fumito Koizumi, Makiko Shimizu, Toshio Ota, Tamer M Fouad, Jie Willey, Hidekuni Kaito, Norihiko Shiraishi, Daisuke Nakashima, Shiro Akinaga, Naoto T Ueno

Affiliations

  1. Fuji Research Park, R&D Division, Kyowa Hakko Kirin Co., Ltd, Shizuoka, Japan.
  2. Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  3. Fujifilm Kyowa Kirin Biologics Co., Ltd., Galashiels, UK.
  4. R&D Division, Kyowa Hakko Kirin Co., Ltd, Tokyo, Japan.
  5. Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1354, Houston, Texas 77030, USA.

PMID: 30083253 PMCID: PMC6066809 DOI: 10.1177/1758835918786858

Abstract

BACKGROUND: KW-2450 is an oral dual insulin-like growth factor-1 receptor/insulin receptor tyrosine kinase inhibitor. We investigated the

METHODS: A series of

RESULTS: Preclinical studies showed KW-2450 and lapatinib act synergistically to induce

CONCLUSIONS: The proposed phase II study of the RP2D for the triple-drug combination did not progress because of anticipated difficulty in patient enrollment and further clinical development of KW-2450 was terminated.

Keywords: HER2-positive; KW-2450; breast cancer; estrogen receptor-positive; lapatinib; letrozole

Conflict of interest statement

Conflict of interest statement: HU, YM, FK, MS, TO, HK, NS, DN, and SA are employees of Kyowa Hakko Kirin Co., Ltd. NTU has a speaker’s agreement with Kyowa Kirin Pharmaceutical Development, Inc. TF h

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