On April 28, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing next-generation multifunctional biotherapeutics, reported that it has completed enrollment in its global HERIZON-BTC-01 pivotal clinical trial evaluating the antitumor activity of zanidatamab monotherapy in patients with previously treated advanced or metastatic HER2-amplified biliary tract cancers (BTC), including gallbladder cancer and cholangiocarcinoma (bile duct cancer) (Press release, Zymeworks, APR 28, 2022, View Source [SID1234613175]). Efficacy and safety results from HERIZON-BTC-01 are expected to be announced by early 2023.
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"Completing enrollment in our first pivotal trial is a tremendous accomplishment for Zymeworks. I’m extremely proud of our team and our collaborators at BeiGene for their hard work in reaching this milestone ahead of expectations," said Neil Josephson, M.D., Chief Medical Officer. "Currently there are limited options for patients with advanced HER2-amplified biliary tract cancer who experience disease progression after front-line therapy. Zanidatamab has the potential to meet the urgent global clinical need for a safe and effective therapy for patients with this difficult to treat cancer."
Biliary tract cancers, including gallbladder cancer and cholangiocarcinoma, account for approximately 3% of all adult cancers and is often associated with a poor prognosis1. Globally, more than 210,000 people are diagnosed with BTC every year2 and most patients (> 65%) with BTC are diagnosed with tumors that cannot be removed surgically. The human epidermal growth factor receptor 2 (HER2) is a well-described target for anti-cancer therapy. About 5% to 19% of patients with BTC have tumors that express HER23, suggesting that these patients may have the potential to benefit from HER2-targeted therapy. Currently no HER2-targeted therapy has been approved for the treatment of BTC.
HERIZON-BTC-01 is a global, multicenter, open-label, single-arm study (NCT04466891) with a primary endpoint of confirmed objective response rate (ORR) by independent central review (ICR) per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints are duration of response (DOR), proportion of subjects with a DOR ≥16 weeks, disease control rate (DCR), progression-free survival (PFS), overall safety (OS) and safety. HER2 amplification, as determined by in situ hybridization (ISH) in tumor tissue, was an inclusion criterion for all subjects enrolled into the two study cohorts: Cohort 1, the primary efficacy cohort, with tumor tissue showing HER2 immunohistochemistry (IHC) 2+ or 3+ staining, and cohort 2 with tumor tissue showing HER2 IHC 0 or 1+ staining. The study was initiated in July 2020 and has active sites in North America, Asia Pacific, Europe and South America.
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. Zanidatamab’s unique binding properties result in multiple mechanisms of action including HER2 -receptor clustering, internalization, and downregulation; inhibition of growth factor-dependent and -independent tumor cell proliferation; antibody-dependent cellular cytotoxicity and phagocytosis; and complement-dependent cytotoxicity. Zanidatamab is currently being evaluated in two pivotal clinical trials, one for the first-line treatment of advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (HERIZON-GEA-01) and one for previously treated HER2-amplified biliary tract cancer (HERIZON-BTC-01). Zanidatamab is also being evaluated in several Phase 2 clinical trials for HER2‑expressing gastroesophageal, colorectal, and breast cancers. The FDA has granted zanidatamab Breakthrough Therapy designation for patients with previously treated HER2 gene-amplified biliary tract cancer, as well as two Fast Track designations, one as monotherapy for refractory biliary tract cancer and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma. 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 received Break Through Designation from the Center of Drug Evaluation (CDE) in China for treating patients with biliary tract cancer who have failed prior systemic therapies. Zanidatamab has also received Orphan Drug designations from the FDA as well as the European Medicines Agency for the treatment of biliary tract and gastric cancers.
Zymeworks has an existing intermediate-size Expanded Access Protocol (EAP) for use of zanidatamab in patients with HER2-positive advanced solid tumors who are not eligible for other zanidatamab clinical trials, and who in the opinion of the treating oncologist, would potentially benefit from treatment with zanidatamab. Additional information is available on our website at View Source
About the Zymeworks-BeiGene Collaboration
In November 2018, Zymeworks and BeiGene entered into license and collaboration agreements in which BeiGene was granted an exclusive license for the research, development, and commercialization of zanidatamab and ZW49 in Asia (excluding Japan), Australia, and New Zealand. The companies are collaborating on joint global development for selected indications, with the goal of developing zanidatamab and ZW49 worldwide across multiple HER2-expressing cancers and lines of therapy.