On December 1, 2020 Zymeworks Inc. (NYSE:ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported that its partner, BeiGene, Ltd., has dosed the first patient in South Korea in a pivotal, single-arm clinical trial of zanidatamab (formerly ZW25) monotherapy in patients with advanced or metastatic HER2-amplified biliary tract cancer (BTC) (Press release, Zymeworks, DEC 1, 2020, View Source [SID1234572047]). Zymeworks will receive a US$10 million payment under its collaboration with BeiGene as a result of the achievement of this development milestone.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Patients with biliary tract cancer generally have a poor prognosis and few treatment options," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "While BTC occurs in patients throughout the world, the incidence is particularly high in Asia. Our collaboration with BeiGene expands the potential of zanidatamab to help address this global unmet need."
Zymeworks and BeiGene are progressing the opening of multiple clinical trial sites in support of the global registration-enabling Phase 2b clinical trial of zanidatamab in patients with HER2-amplified BTC. In the Asia region, multiple sites are open for enrollment in South Korea, and in China all sites have been selected with enrollment anticipated to begin in the first quarter of 2021.
This global zanidatamab study may enable the submission of a Biologics License Application by Zymeworks in the United States as early as 2022. Multiple clinical sites are now open to enrollment in the U.S., Europe, and Asia, with additional sites planned, including in Canada and South America.
"We are pleased to have been able to initiate this important clinical trial and hope that it may help contribute to improving the lives of patients with advanced or metastatic BTC and HER2 amplification," said Lai Wang, Ph.D., Senior Vice President, Head of Global Research and APAC Clinical Development at BeiGene. "As our collaboration with Zymeworks continues, this trial may help lead to expedited global regulatory approvals, including in China and South Korea."
This pivotal Phase 2b clinical trial is a global, multicenter, open-label, single-arm study designed to evaluate the antitumor activity of zanidatamab monotherapy in patients with HER2-amplified, inoperable and advanced or metastatic BTC, including gallbladder cancer and cholangiocarcinoma (Phase 2:NCT04466891). Patients must have received at least one prior gemcitabine-containing systemic chemotherapy regimen for advanced disease and have experienced disease progression after (or developed intolerance to) their most recent prior therapy. The primary endpoint of the study is the confirmed objective response rate (ORR) by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Ongoing clinical trials are evaluating zanidatamab in first-line HER2-positive gastroesophageal adenocarcinoma (GEA) in combination with standard of care chemotherapy (Phase 2: NCT03929666) as well as in combination with the oral CDK4/6 inhibitor palbociclib (Ibrance, Pfizer) and fulvestrant in advanced HER2-positive, HR-positive breast cancer (Phase 2: NCT04224272). Zymeworks, in collaboration with BeiGene, plans to develop zanidatamab as a potential first-line treatment for patients with HER2-positive GEA. BeiGene is also conducting a two-arm Phase 1b/2 trial evaluating zanidatamab in combination with chemotherapy as a first-line treatment for patients with metastatic HER2-positive breast cancer and in combination with chemotherapy and BeiGene’s PD-1-targeted antibody tislelizumab as a first-line treatment for patients with metastatic HER2-positive GEA (NCT04276493). In addition, an ongoing Phase 1 trial is evaluating the safety and antitumor activity of zanidatamab as a single agent and in combination with chemotherapy in HER2-expressing cancers that have progressed after prior standard of care treatments, including HER2-targeted agents (Phase 1: NCT02892123).
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 registration-enabling 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 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, as well as Orphan Drug designation for the treatment of gastric cancer from the European Medicines Agency.
About Biliary Tract Cancer
Biliary tract cancer (BTC), including gallbladder cancer and cholangiocarcinoma (bile duct cancer), accounts for approximately 3% of all adult cancers and is associated with a poor prognosis. Globally, more than 210,000 people are diagnosed with BTC every year. Most patients (> 65%) with BTC are diagnosed with tumors that cannot be removed surgically, and even those patients who undergo potentially curative surgery have a high recurrence rate. Treatment options are limited for patients with advanced BTC who experience disease progression after front-line chemotherapy.
The human epidermal growth factor receptor 2 (HER2) is a well-described target for anti-cancer therapy. Tumor cells that produce a higher than normal level of HER2 tend to grow more quickly and spread to other parts of the body. About 5% to 19% of patients with BTC have tumors that express HER2, suggesting that these patients may potentially benefit from HER2-targeted therapy. Currently no HER2-targeted therapy has been approved for the treatment of BTC.
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.