Developing a HER2 low companion diagnostic test

TOKYO, MUNICH and BASKING RIDGE, N.J.—Daiichi Sankyo Company, Ltd. announced yesterday that it has entered into an agreement with Roche to collaborate on the development of a new HER2 low companion diagnostic test.

Under the terms of the agreement, Roche will seek to develop, manufacture and commercialize worldwide an immunohistochemistry (IHC) companion diagnostic test with the goal of identifying patients with HER2 low expressing metastatic breast cancer to be enrolled into a pivotal Phase 3 study evaluating the safety and efficacy of [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC). Specific financial terms of the agreement have not been disclosed.

[Fam-] trastuzumab deruxtecan is the lead product in the investigational ADC franchise of the Daiichi Sankyo Cancer Enterprise. ADCs deliver cytotoxic chemotherapy 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, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 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.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. [Fam-] trastuzumab deruxtecan is in Phase 3 development versus ado-trastuzumab emtansine (T-DM1) (DESTINY-Breast03), and versus investigator’s choice post T-DM1 (DESTINY-Breast02) for HER2 positive metastatic breast cancer; pivotal Phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01); pivotal Phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); Phase 2 development for HER2 expressing advanced colorectal cancer; Phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and Phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1, and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1, by the US Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labor and Welfare (MHLW).

“This agreement is an important milestone in our [fam-] trastuzumab deruxtecan development program as we continue to evaluate its potential as a treatment strategy for breast cancers that express low levels of HER2, as there are currently no approved anti-HER2 therapies available for these patients,” said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global team leader, Oncology research and development, Daiichi Sankyo. “We look forward to collaborating with Roche, a global developer of companion diagnostic tests, and leveraging the market-leading HER2 (4B5) assay to identify HER2 low patients and help redefine this biomarker as a cell surface target.”