Micrograph showing a lymph node invaded by ductal breast carcinoma and with extranodal extension of tumour. Credit: Nephron / commons.wikimedia.org.

Zymeworks and ALX Oncology have dosed the first subject in the Phase Ib/II clinical trial of Zanidatamab plus evorpacept (ALX148) in patients with advanced human epidermal growth factor receptor 2 (HER2)-expressing breast cancer and various solid tumours.

Zanidatamab is a HER2‑targeted bispecific antibody of Zymeworks, while evorpacept is a Cluster of Differentiation 47 (CD47) blocker of ALX.

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Based on the Azymetric platform of Zymeworks, zanidatamab can attach concurrently to two non-overlapping epitopes of HER2, which is called biparatopic binding.

Evorpacept is a CD47 blocking treatment that merges an increased-affinity CD47 binding domain with an Fc domain that is not activated.

The open-label, multicentre trial carried out by Zymeworks will assess the safety and efficacy of zanidatamab plus evorpacept in patients with advanced HER2-positive breast cancer, HER2-low breast cancer and other non-breast HER2-expressing solid tumours.

This partnership builds on the potential antitumor activity of evorpacept plus zanidatamab demonstrated in trials involving advanced HER2‑positive gastric or gastroesophageal junction cancer patients.

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Adding CD47 blockade aids in boosting the immunotherapeutic properties of zanidatamab.

Furthermore, it can potentially be useful to a wide range of patients, including those with advanced HER2‑expressing breast cancer and other HER2‑expressing tumours.

Zymeworks noted that zanidatamab, in combination with evorpacept, can possibly boost the immune clearance of HER2-expressing cancer cells.

The treatment can merge a biparatopic antibody capable of binding at increased density as compared to monospecific antibodies with a molecule that hinders CD47 on the same targeted tumour cells.

Zanidatamab is currently being analysed in various Phase I, Phase II and pivotal trials across the globe as a targeted therapy option for HER2-expressing solid tumour patients.

ALX is evaluating evorpacept along with various anti-tumour agents in multiple international Phase I as well as Phase II trials for a variety of hematologic and solid cancers.