Zymeworks Inc. announced new clinical data for the HER2-targeted bispecific antibody zanidatamab in both HER2-positive breast cancer and gastric/gastroesophageal junction adenocarcinoma. The data are being presented in two separate poster sessions at the American Society of Clinical Oncology (ASCO) Annual Meeting June 3-7, 2022 in Chicago, IL. Over one million patients are diagnosed with gastric cancer every year worldwide, and it is the fourth most common cause of cancer-related deaths.

Human epidermal growth factor receptor 2 (HER2)-positive disease accounts for 15–25% of gastric cancers. For these patients, trastuzumab in combination with chemotherapy is the global standard of care treatment but with an expected overall survival of less than 18 months, there remains a significant unmet need. In 33 response-evaluable patients with advanced HER2-positive gastric/gastroesophageal junction adenocarcinoma treated with zanidatamab and tislelizumab in combination with the CAPOX chemotherapy regimen the cORR was 75.8% (25/33).

The DCR was 100% (33/33) and duration of response (DOR) ranged from 2.1+ to 18.2+ months. Twenty patients (61%) remain on study at the time of data cut-off. In addition, the data demonstrate that zanidatamab and tislelizumab in combination with the CAPOX 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 from 33% to 21%. Immune mediated adverse events occurred in 27% of patients, including = Grade 3 events in 21% of patients and resulted in discontinuation of tislelizumab in 3 patients (9%). This manageable safety profile compares favorably to the current standard of care as well as to emerging treatments and is consistent with previous reports.