Data for patritumab deruxtecan (U3-1402; Daiichi Sankyo) and fam-trastuzumab deruxtecan-nxki* (Enhertu®; Daiichi Sankyo/AstraZeneca), two antibody-drug conjugates (ADC) based on Daiichi Sankyo’s proprietary DXd ADC technology, will be presented at the 2020 European Society of Medical Oncology (ESMO) Virtual Scientific Program to be held September 19-21, 2020 (#ESMO20).

The late-breaking presentation of patritumab deruxtecan, an investigational first-in-class HER3 directed ADC, will feature an analysis that includes the first safety and efficacy results from the dose-expansion cohort of a phase I clinical trial in patients with EGFR mutated unresectable advanced non-small cell lung cancer (NSCLC) previously treated with a tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Data from the HER2 low expression exploratory cohorts of the pivotal phase II DESTINY-Gastric01 study of fam-trastuzumab deruxtecan-nxki in patients with previously treated advanced gastric or gastroesophageal junction cancer will also be presented.[1][2][3][4]

“We look forward to presenting these new results from the ongoing phase 1 study of patritumab deruxtecan in patients with previously treated, advanced EGFR mutated NSCLC, which reflect encouraging progress in the clinical development of this HER3 directed therapy,” said Gilles Gallant, BPharm, Ph.D., FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo.

“These data, along with the current body of research across our ADC portfolio, demonstrate significant progress in our oncology pipeline and underscore our commitment to translating our DXd ADC technology into potential new treatment options for patients across a number of tumor types,” Gallant added.

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ADC Portfolio
Patritumab deruxtecan and trastuzumab deruxtecan are two ADCs in Daiichi Sankyo’s
portfolio of DXd ADCs, which currently consists of five antibody-drug conjugates (ADCs) with five in clinical development across multiple types of cancer. Other ADCs in this portfolio of investigational agents include DS-1062, a TROP2 directed ADC, which is being jointly developed and commercialized globally with AstraZeneca, DS-7300, a B7-H3 directed ADC, and DS-6157, a GPR20 directed ADC, which are being developed through a strategic research collaboration with Sarah Cannon Cancer Institute.

Each of these ADC is engineered using Daiichi Sankyo’s proprietary and portable DXd ADC technology to target and deliver chemotherapy inside cancer cells that express a specific cell surface antigen. Each ADC consists of a monoclonal antibody attached by a stable tetrapeptide-based linker to a topoisomerase I inhibitor payload (chemotherapy) with a customized drug to antibody ratio (DAR) to optimize the risk-benefit ratio for the intended patient population.

2020 European Society of Medical Oncology (ESMO) Virtual Scientific ProgramPresentation Details
Patritumab deruxtecan (HER3 ADC)
Efficacy and safety of patritumab deruxtecan (U3-1402), a novel HER3 directed antibody drug conjugate, in patients with EGFR-mutated (EGFRm) NSCLCLate-Breaker Mini-Oral Presentation (#LBA62): H Yu, et al.; September 18, 2020 at 9:00 a.m. CEST
Trastuzumab deruxtecan (HER2 ADC)
Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2 low, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: results of the exploratory cohorts in the phase 2, multicenter, open-label DESTINY-Gastric01 studyMini-Oral Presentation (#1422MO): Yamaguchi, et al. Gastrointestinal tumors, non-colorectal; September 18, 2020 at 9:00 a.m. CEST
A phase 1b/2, multicenter, open-label, dose-escalation and dose-expansion study evaluating trastuzumab deruxtecan (T-DXd; DS-8201) monotherapy and combinations in patients with HER2-overexpressing gastric cancer (DESTINY-Gastric03) [TiP]E-poster Presentation (#1500TiP): Janjigian, et al.; September 17, 2020 at 9:00 a.m. CEST
Patient preferences for HER2-targeted treatment of advanced or metastatic breast cancer in the United StatesE-poster Presentation (#340P): Mansfield, et al.; September 17, 2020 at 9:00 a.m. CEST
Risk factors for interstitial lung disease in patients treated with trastuzumab deruxtecan from two interventional studiesE-poster Presentation (#289P): Powell, et al.; September 17, 2020 at 9:00 a.m. CEST
Artificial intelligence analysis of advanced breast cancer patients from a phase 1 trial of trastuzumab deruxtecan (T-DXd): HER2 and histopathology features as predictors of clinical benefitE-poster Presentation (#286P): Modi, et al.; September 17, 2020 at 9:00 a.m. CEST

Fam-trastuzumab deruxtecan-nxki (Enhertu®; 5.4 mg/kg) is approved in the United States and Japan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial. Trastuzumab deruxtecan-nxki has not been approved in the European Union, or countries outside of the U.S. and Japan for any indication.

Drug Description
Fam-trastuzumab deruxtecan-nxki (Enhertu®; 5.4 mg/kg) [Drug description]

Clinical trials
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01] – NCT03329690
Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2+ Gastric Cancer (DESTINY-Gastric03) (DG-03) – NCT04379596

Highlights of prescribing information
Fam-trastuzumab deruxtecan-nxki (Enhertu®)[Prescribing Information]

[1] Koganemaru S, Kuboki Y, Koga Y, et al. U3-1402, a Novel HER3-Targeting Antibody-Drug Conjugate, for the Treatment of Colorectal Cancer. Mol Cancer Ther. 2019;18(11):2043-2050. doi:10.1158/1535-7163.MCT-19-0452
[2] Hashimoto Y, Koyama K, Kamai Y, et al. A Novel HER3-Targeting Antibody-Drug Conjugate, U3-1402, Exhibits Potent Therapeutic Efficacy through the Delivery of Cytotoxic Payload by Efficient Internalization. Clin Cancer Res. 2019;25(23):7151-7161. doi:10.1158/1078-0432.CCR-19-1745
[3] Yonesaka K, Takegawa N, Watanabe S, et al. An HER3-targeting antibody-drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC. Oncogene. 2019;38(9):1398-1409. doi:10.1038/s41388-018-0517-4
[4] Haratani K, Yonesaka K, Takamura S, et al. U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation. J Clin Invest. 2020;130(1):374-388. doi:10.1172/JCI126598

Featured Image: ESMO 2019 Congress being held in Barcelona, Spain, September 27 – October 1, 2019. Courtesy European Society for Medical Oncology (ESMO). Used with Permission.

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