On July 28, 2021 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported the first patient has been dosed with zanidatamab in combination with Tukysa (tucatinib) and capecitabine in a new cohort of a Phase 1 trial for HER2-positive breast cancer patients with locally advanced (unresectable) and/or metastatic disease (Press release, Zymeworks, JUL 28, 2021, View Source [SID1234585295]).

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"Recent clinical trials have demonstrated the benefit of combining tucatinib with trastuzumab and chemotherapy in patients with metastatic HER2-positive breast cancer," said Neil Josephson, M.D., Interim Chief Medical Officer at Zymeworks. "Given the antitumor activity of zanidatamab observed across a range of HER2-overexpressing tumors and preclinical studies demonstrating improved anti-tumor activity of zanidatamab compared to trastuzumab, we believe the combination of zanidatamab with tucatinib and chemotherapy has the potential to be an impactful treatment for patients with advanced HER2-positive breast cancer, including those with brain metastases." Josephson added, "this new study cohort complements our ongoing trials with zanidatamab in combination with other standard of care treatment regimens and supports our goal of establishing zanidatamab as the foundational therapy for HER2-expressing cancers."

Zanidatamab binds to HER2 across a range of expression levels and has demonstrated multiple mechanisms of action including the formation of receptor clusters, resulting in receptor internalization and downregulation that affect signal transduction. In addition, zanidatamab potently activates the immune system to elicit antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity. Tucatinib is a tyrosine kinase inhibitor of HER2 and helps prevent the cancer cells from growing. Several studies have shown that combining agents that target HER2 with complementary mechanisms of action result in proven efficacy. The U.S. Food and Drug Administration last year approved tucatinib in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced forms of HER2-positive breast cancer that can’t be removed with surgery, or has spread to other parts of the body, including the brain, and who have received one or more prior treatments.

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. The FDA has granted

Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancer (BTC), and two Fast Track designations to zanidatamab, one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as intensive FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations for the treatment of biliary tract, gastric and ovarian cancers from the FDA, as well as Orphan Drug designation for the treatment of biliary tract and gastric cancer from the European Medicines Agency.