Phase 1 Study of Treatment for Advanced HER2-Positive Cancers Gets Underway

Phase 1 Study of Treatment for Advanced HER2-Positive Cancers Gets Underway

A Phase 1 clinical trial assessing the safety and efficacy of the anti-HER2 antibody ZW25 in advanced or metastatic HER2-positive cancers has just dosed its first patient, according to a recent announcement by Zymeworks, the therapy’s manufacturer.

“We are excited to have begun enrollment in this initial study of ZW25,” Diana Hausman, Zymeworks’ chief medical officer, said in a press release. “No approved HER2-targeted therapies exist for many patients with HER2-expressing cancers and with its unique mechanism of action, ZW25 has the potential to address this significant unmet need.”

The trial (NCT02892123), which is currently recruiting participants, is an open-label, single-group study evaluating the safety and tolerability of ZW25 in patients with locally advanced, unresectable, or metastatic HER2-expressing cancers, including ovarian, breast, gastric, lung cancers. (More information about the trial is available on its clinical website.)

Each of the 30 patients expected to enter the study will receive once weekly, intravenous, escalating doses of ZW25, which will allow the researchers to identify the highest dose that can be administered without unacceptable side effects. Investigators are also seeking to determine the drug dose associated with optimal biologic activity.

Zymeworks is developing protein-based therapeutics for the treatment of cancer, autoimmune, and inflammatory diseases. ZW25, its lead therapeutic based on its Azymetric platform, is a novel bi-specific antibody that targets two different specific sites of the HER2 protein.

Compared to the current available therapeutics, ZW25 presents enhanced activity due to its multiple mechanisms of action: enhanced antibody-mediated cell death, increased blockage of HER2-induced cell growth, and increased removal of the surface-expressed HER2 protein due to enhanced HER2 internalization upon binding to ZW25.

Overall, ZW25 has a high affinity to HER2 protein, leading to an increased capability to block HER2 pro-tumor activity. This makes ZW25 a best-in-class HER-targeting antibody, with preclinical data showing its ability to treat HER2 low-expressing tumors that are not eligible for other HER2-targeted therapies.

HER2 is overexpressed on the surface of many cancerous cells. Consistently, ZW25 has shown anti-tumor activity in several cancer models, including ovarian, breast, gastric/gastroesophageal, and non-small cell lung cancers. In experimental animal models of HER2-expressing cancers, ZW25 presented an acceptable safety profile.

ZW25 has been designated an Orphan Drug by the U.S. Food and Drug Administration (FDA) for the treatment of ovarian cancer.