Zymeworks has initiated a Phase II trial to assess the efficacy of ZW25 as a combination therapy for previously-treated locally advanced and/or metastatic HER2-positive, HR-positive breast cancer.

The Canadian biotech company entered a partnership to test its HER2-targeted bispecific antibody ZW25 in combination with Pfizer’s Ibrance (palbociclib), an oral CDK4/6 inhibitor, and hormone therapy fulvestrant.

The Phase II open-label, two-part study will include up to 76 patients.

In part one, the trial will assess the safety and tolerability of ZW25 as a combination therapy, as well as determine the recommended doses (RD) of ZW25 and palbociclib.

The study will then assess anti-tumour activity at the RD level.

The ZW25 study will be conducted across multiple sites in the US and Canada, with an expansion to Spain also under consideration.

Zymeworks chief medical officer Diana Hausman said: “The initiation of this Phase II trial and collaboration with Pfizer mark significant milestones in our progress towards establishing ZW25 as the foundational HER2 therapy in multiple regimens across breast and other cancers.

“Together, ZW25 and palbociclib have the potential to improve anti-tumour activity and minimise side effects for people living with advanced HER2‑positive, HR-positive breast cancer.”

Based on Zymeworks’ Azymetric platform, ZW25 is a bispecific antibody developed to treat patients with solid tumours that express HER2.

The candidate is currently tested for the treatment of HER2‑expressing cancers, including biliary tract, gastroesophageal adenocarcinoma (GEA), breast, colorectal and gynecologic cancers.

Under the Phase I trial, which is also underway, ZW25 is being evaluated as a single agent and in combination with chemotherapy.