Jazz Pharmaceuticals plc and Zymeworks Inc. announced tolerability and efficacy results, including the first overall survival (OS) data, from a Phase 2 trial examining zanidatamab, an investigational HER2-targeted bispecific antibody, in combination with chemotherapy, in first-line patients with HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA). The preliminary results showed that, at the time of analysis, the median OS had not yet been reached with a median duration of study follow-up of 26.5 months. The 18-month overall survival rate was 84% [95% confidence interval (CI): 68%, 93%]. Trial Results The data include efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with advanced HER2-expressing mGEA, which is comprised of gastric, esophageal and gastroesophageal junction (GEJ) patients. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with mGEA were enrolled from 15 sites
across the United States, Canada and South Korea, and patients were administered zanidatamab with physician's choice of chemotherapy treatment (standard first-line combination therapy). The data demonstrated zanidatamab combined with standard chemotherapy is a highly active treatment regimen for first-line therapy of HER2-positive mGEA. In 42 patients evaluable for OS receiving zanidatamab in combination with chemotherapy, the 18-month OS rate was 84% (95% CI: 68%, 93%), the 12-month OS rate was 88% (95% CI: 73%, 95%), and the median overall survival had not yet been reached (with 26.5 months median duration of study follow-up). Treatment with
zanidatamab resulted in a confirmed objective response rate (cORR) of 79% (95% CI: 63-90%), a disease control rate (DCR) of 92% (95% CI: 79-98%), with three patients achieving complete response among 38 response-evaluable patients. The median duration of response was 20.4 months (95% CI: 8.3-NE) with a median progression-free survival (mPFS) of 12.5 months (95% CI: 7.1-NE) with 17 patients having an ongoing response at the time of data cutoff. The regimen was manageable, tolerable and consistent with the observed safety profiles reported for other standard combination regimens for patients with HER2-positive GEA. Data were presented in a poster session entitled Zanidatamab + Chemotherapy as First-Line Treatment for HER2-expressing Metastatic Gastroesophageal Adenocarcinoma (mGEA) during the American Society of Clinical Oncology's Gastrointestinal Cancers Symposium (ASCO GI) taking place in San Francisco. The presentation is available to conference registrants on the ASCO GI conference website (Abstract Number 347), and will be available to the general public on Zymeworks' website.Zymeworks continues to enroll patients in the Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing mGEA. About Zanidatamab Zanidatamab is an investigational bispecific antibody, based on Zymeworks' Azymetric(TM) 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, along with collaborators Jazz and BeiGene Ltd. (BeiGene), are developing zanidatamab in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line GEA. Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and
GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.