Project 466229

Patients with advanced stomach or esophageal cancer that is not treatable by surgical removal and which has high amounts of human epidermal growth factor receptor Type 2 (aka HER2) on the surface of their tumour cells, receive the anti-HER2 drug trastuzumab added to chemotherapy as standard of care, with the benefit that the addition of trastuzumab extends their survival. Investigation of other drugs that target HER2 and other cancer surface proteins simultaneously, or that link HER2 with another anti-cancer drug, have not shown benefit for these patients to-date. When these patients experience further growth of their cancer due to resistance, their next option for treatment is a combination of a toxic chemotherapy and a drug which binds to another cancer surface protein known as the vascular endothelial growth factor receptor type 2 (VEGFR2). Zanidatamab is a new type of antibody/drug that targets HER2, but offers the possible benefit over trastuzumab that it can not only bind slightly different versions of HER2, but it can also bind two HER2 receptors simultaneously. This means that zanidatamab may do a better, more efficient job of blocking HER2 receptors and may therefore have better effect in slowing tumour growth, or even causing tumour cell death. Early trials of zanidatamab in patients with stomach and esophageal cancers expressing HER2 have yielded very promising results both in terms of the effect on their cancers as well as the tolerability of zanidatamab. The current phase II study is seeking to determine whether there is sufficient early evidence that adding zanidatamab to the standard of care therapy for those patients who have become resistant to trastuzumab can better slow the growth of their tumours in order to proceed with a definitive, confirmatory phase III study which would be expected to lead to the approval of zanidatamab as standard of care treatment of these patients.