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zymeworks Zymeworks Launches Global Phase 3 Zanidatamab Trial in First - Line HER2 - Positive Gastroesophageal Adenocarcinoma ( GEA ) November 9 , 2021 • HERIZON - GEA - 01 study is now open and enrolling patients to evaluate zanidatamab and chemotherapy with or without tislelizumab , versus standard of care • Phase 2 data demonstrate potential benefit of zanidatamab in first - line GEA , with response rates and durability that compare favorably to both current standard of care and emerging treatments ● Study design enables a potential supplemental biologics license application ( BLA ) for zanidatamab in first - line HER2 - positive GEA as early as 2024 • Zymeworks will host a conference call and webcast at 4:15 pm ET today to discuss the HERIZON - GEA - 01 Phase 3 trial design as well as the commercial strategy in HER2 - positive gastrointestinal cancers VANCOUVER , British Columbia -- ( BUSINESS WIRE ) -- Nov . 9 , 2021-- Zymeworks Inc. ( NYSE : ZYME ) , a clinical - stage biopharmaceutical company developing multifunctional biotherapeutics , today announced , together with its partner BeiGene , the launch of HERIZON - GEA - 01 . This is a randomized , global Phase 3 study evaluating Zymeworks ' investigational HER2 -targeted bispecific antibody , zanidatamab , plus chemotherapy , with or without BeiGene's anti - PD -1 - targeted antibody tislelizumab , versus standard of care ( trastuzumab plus chemotherapy ) , for the first - line treatment of metastatic HER2 - postive GEA . " We are incredibly excited to launch our second pivotal , and first Phase 3 clinical trial for zanidatamab , HERIZON - GEA - 01 , " said Ali Tehrani , Ph.D. , Zymeworks ' President & CEO . " Gastrointestinal cancers have significant unmet patient need and we have the opportunity to help a large and growing patient population . With two potential Biologics License Applications over the next 3 years , we believe zanidatamab has the potential to achieve blockbuster status and position Zymeworks as the leader in the treatment of HER2 - positive Gl cancers . " The primary objective of the HERIZON - GEA - 01 study is to evaluate the efficacy and safety of zanidatamab in combination with physician's choice chemotherapy [ CAPOX ( capecitabine / oxaliplatin ) or FP ( 5FU / cisplatin ) ] with or without tislelizumab compared to trastuzumab plus physician's choice chemotherapy in subjects with advanced or metastatic HER2 - positive GEA . Primary endpoints are progression - free survival by RECIST 1.1 , assessed by blinded independent central review , and overall survival . The HERIZON - GEA - 01 study seeks to enroll approximately 700 patients at approximately 300 sites across 38 countries . BeiGene will oversee trial sites in Asia ( excluding Japan ) , Australia and New Zealand , and Zymeworks will oversee trial sites in the rest of the world , including North and South America , Japan , Europe , Middle East , and Africa . " We are pleased the HERIZON - GEA - 01 study has begun enrollment and our aim is to establish zanidatamab as the foundational agent of a new standard of care with tislelizumab for the first - line treatment of HER2 - positive GEA , " said Neil Josephson , M.D. , Zymeworks ' Interim Chief Medical Officer . " Based on the study design , we expect to have progression - free survival data as soon as 2024 , which could enable submission of a supplemental Biologics License Application that same year . " GEA is the fifth most common cancer worldwide and approximately 20 percent of patients diagnosed with this form of cancer are HER2 - positive . HER2 - positive GEA has high morbidity and mortality and patients are urgently in need of new treatment options . " The encouraging zanidatamab Phase 2 data support its further investigation with tislelizumab in this Phase 3 HERIZON - GEA - 01 trial in first - line HER2 - positive gastroesophageal adenocarcinomas , " said Yong ( Ben ) Ben , M.D. , Chief Medical Officer , Solid Tumors , at BeiGene . " We are excited to continue our collaboration with Zymeworks as we strive to address the unmet medical needs in this patient population by accelerating the development of zanidatamab . " Phase 2 Study Results In September , Zymeworks presented data at the European Society for Medical Oncology Annual Meeting from a Phase 2 clinical study of 36 patients with HER2 - expressing GEA who received zanidatamab in combination with either CAPOX ( n = 14 ) , FP ( n = 2 ) , or mFOLFOX6 ( 5FU / leucovorin / oxaliplatin ; n = 20 ) . None of the patients had received prior HER2 - targeted therapies . In 28 response - evaluable patients with metastatic HER2 - positive GEA , zanidatamab plus chemotherapy resulted in a confirmed objective response rate ( CORR ) of 75 % and disease control rate ( DCR ) of 89 % overall , with a CORR of 93 % and DCR of 100 % in the proposed Phase 3 regimen of zanidatamab and CAPOX / FP . All patients except one experienced a decrease in their tumor size . Across all treatment regimens , the median duration of response is 16.4 months and the median progression - free survival is 12.0 months , with 61 % of patients still on study at the time of data cutoff . In addition , the data demonstrate that zanidatamab plus chemotherapy is generally well tolerated , with the majority of treatment - related adverse events ( TRAES ) considered mild to moderate in severity ( Grade 1 or 2 ) . The most common grade ≥ 3 TRAE was diarrhea , which was manageable in the outpatient setting ; introduction of prophylactic loperamide reduced the incidence in cycle 1 from 44 % to 18 % . No severe ( grade ≥ 3 ) infusion related reactions or cardiac events were observed .