NEW YORK – Zymeworks and ALX Oncology on Tuesday said the first advanced cancer patient has received treatment in a Phase Ib/II clinical trial of Zymeworks' HER2-targeting agent zanidatamab combined with ALX's CD47-targeting evorpacept.
The trial, conducted by Zymeworks, is designed to evaluate the investigational drug combination in subgroups of HER2-expressing cancers. Part I and II of the trial will include patients with advanced, previously treated HER2-positive breast cancer, including those with low HER2-expressing tumors, defined as cancers that express HER2 with immunohistochemistry, or IHC, staining of 1+ or 2+.
Part II of the trial will enroll patients with other types of solid tumors, such as HER2-positive gastroesophageal cancer and HER2-overexpressing non-breast cancers, defined as those with IHC staining of 3+ or IHC 2+ with positive in situ hybridization results.
The drug development partners decided to combine the CD47 inhibitor evorpacept with the HER2-targeting bispecific antibody zanidatamab hoping to overcome cancer cells' resistance to immune clearance by targeted therapeutic antibodies. CD47 acts as a checkpoint inhibitor to macrophages, making CD47-expressing cells potentially resistant to zanidatamab. Accordingly, blocking CD47 with evorpacept could enhance zanidatamab's ability to clear HER2-expressing cancer cells. Earlier trials of evorpacept combined with a HER2-targeting antibody has shown promising activity in patients with advanced HER2-positive gastric or gastroesophageal junction cancer.
The companies aim to enroll around 90 patients in the trial, and assess safety, toxicity, and overall response rates as primary endpoints. Secondary endpoints will include disease control rate, clinical benefit rate, duration of response, progression-free survival, and overall survival.