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Daiichi Sankyo Initiates Phase 1 Study of U3-1402 in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

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February 06, 2018

  • Phase 1 study to examine safety and tolerability of U3-1402, a potential first-in-class HER3-targeting antibody drug conjugate (ADC), in patients with metastatic EGFR-mutated NSCLC

  • Patients with EGFR-mutated NSCLC who experience disease progression during EGFR tyrosine kinase inhibitor therapy have limited treatment options to control the disease

  • Second phase 1 study of U3-1402 utilizes Daiichi Sankyo’s proprietary ADC technology


Tokyo, Basking Ridge, NJ, and Munich – (February 6, 2018) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) announced today that the first patient has been dosed in a phase 1 study evaluating the safety and tolerability of U3-1402, an investigational and potential first-in-class HER3-targeting antibody drug conjugate (ADC), in patients with metastatic or unresectable epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) whose disease has progressed while taking an EGFR tyrosine kinase inhibitor (TKI).

Treatment with EGFR TKIs such as erlotinib, gefitinib, or afatinib is used as first-line therapy for metastatic EGFR-mutated NSCLC.1,2,3,4 However, patients eventually develop resistance to these treatments, typically experiencing disease progression within a year.1,2,3,4 More than half of these patients develop resistance with a secondary EGFR mutation called T790M, which may be treated with EGFR TKI osimertinib.1,2,3,4 Patients who experience disease progression following EGFR TKI treatment and who have tumors that lack the T790M mutation may be treated with chemotherapy, immunotherapy, or with investigational treatments.3,4

Expression of HER3, a member of the HER family of receptor tyrosine kinases, is believed to play a role in tumor growth and proliferation in many different types of cancer including NSCLC.5 Studies have shown that HER3 overexpression in lung cancer can also be associated with acquired resistance to other EGFR family targeted interventions such as TKIs and anti-EGFR antibody therapies.5 Patients with NSCLC with high levels of HER3 may face a significantly worse prognosis and decreased survival.5,6,7 Currently, there are no approved HER3-targeted therapies.

“While the treatment of metastatic EGFR-mutated NSCLC has significantly improved over the past decade, new treatments are needed that work to overcome resistance associated with current EGFR TKIs,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “In this study, we are exploring whether the smart delivery of chemotherapy with U3-1402 to cancer cells that express HER3 - a known feature of resistance in pre-treated EGFR-mutated NSCLC - could become a new treatment strategy for these patients.”

About the Study

The global, phase 1, open label, two-part study will enroll patients with metastatic or unresectable EGFR-mutated NSCLC whose disease has progressed while taking an EGFR TKI. This includes patients who experienced disease progression during treatment with erlotinib, gefitinib, or afatinib and whose tumors have tested negative for the T790M mutation and patients who experienced disease progression during treatment with osimertinib regardless of T790M status. The primary objectives of the study are to assess the safety and tolerability of U3-1402 and determine the recommended dose for the dose expansion part of the study. The secondary objectives are to characterize the pharmacokinetics of U3-1402 and to evaluate preliminary efficacy by measuring antitumor activity of U3-1402. The study is expected to enroll more than 60 patients at approximately 17 sites globally. For more information about the study, visit

About U3-1402

Part of the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise, U3-1402 is an investigational and potential first-in-class ADC. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, U3-1402 is a smart chemotherapy comprised of a human anti-HER3 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

U3-1402 is currently being evaluated in two phase 1 clinical studies including a phase 1/2 study for HER3-expressing metastatic or unresectable breast cancer and a phase 1 study for metastatic or unresectable EGFR-mutated NSCLC. U3-1402 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise

The vision of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science Franchise, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: DS-8201, an antibody drug conjugate (ADC) for HER2-expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory acute myeloid leukemia (AML) with FLT3-ITD mutations; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit:

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address diversified, unmet medical needs of patients in both mature and emerging markets. With over 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for hypertension and thrombotic disorders, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo research and development is primarily focused on bringing forth novel therapies in oncology, including immuno-oncology, with additional focus on new horizon areas, such as pain management, neurodegenerative diseases, heart and kidney diseases, and other rare diseases. For more information, please visit: Daiichi Sankyo, Inc., headquartered in Basking Ridge, New Jersey, is a member of the Daiichi Sankyo Group. For more information on Daiichi Sankyo, Inc., please visit:



  1. Wang J, et al. Onco Targets Ther. 2016; 9:3711-3726.

  2. Zhou C, et al. Journal of Thoracic Oncology. 2015; 11 (2):174-186.

  3. National Comprehensive Cancer Network. NCCN Guidelines NSCLC. 8.2017.

  4. Novello S, et al. Annals of Oncology. 2016; 27 (Supplement 5): v1-v27.

  5. Mujoo K, et al. Oncotarget. 2014;5(21).

  6. Muller-Tidow C, et al. Cancer Res. 2005.

  7. Yi E, et al. Mod Pathol. 1997;10(2):142-8





Refer to

Jennifer Brennan
Daiichi Sankyo, Inc.
+1 908 992 6631 (office)
+1 201 709 9309 (mobile)

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