Zanidatamab in combination with evorpacept has been dosed for the first time in a patient with HER2-low breast cancer.
The first patient has been dosed with the combination of zanidatamab and evorpacept (ALX148) in a phase 1b/2 study evaluating the safety and efficacy of the combination in HER2-low breast cancer, and additional non-breast HER2-expressing solid tumors, according to a press release issued by Zymeworks, Inc.1
Initiation of this study stems from a collaboration between Zymeworks, Inc and ALX Oncology Holdings Inc, which together aim to build upon the encouraging clinical activity previously observed when evorpacept was combined with a HER2-targeted antibody to treat advanced HER2‑positive gastric or gastroesophageal junction cancer (ASPEN-01, NCT03013218).2
In 18 patients with HER2-positive gastric cancer treated in the second-line setting, treatment with evorpacept in combination with trastuzumab (Herceptin) and chemotherapy achieved an objective response rate (ORR) of 72% and an estimated 12-month overall survival rate of 76%.
Compared with historic controls, these data suggested an improved benefit when adding an anti-HER2 agent to evorpacept. With evorpacept, the immunotherapeutic effects of zanidatamab can be enhanced and provide benefit for patients HER2-exressing advanced solid tumors, including those with HER2-positive breast cancers.
In the open-label study (NCT05027139), approximately 93 patients will be enrolled. In part 1 of the study, investigators will assess the incidence of dose-limiting toxicities, the incidence of adverse events (AEs), and the incidence of laboratory abnormalities as coprimary end points. The part 2 primary end point is the confirmed objective response rate (ORR). The secondary end points of disease control rate, clinical benefit rate, duration of response, progression-free survival (PFS), PFS 6, overall survival (OS), the incidence of AEs, maximum serum concentration of the combination therapy, and the incidence of anti-drug antibodies will also be evaluated.1
To be eligible, patients must have a locally advanced and/or metastatic HER2-expressing cancer and have progressed after or during their most recent systemic regimen of treatment for advanced disease. Patients are also required to have measurable disease per RECIST v1.1, confirmed ER protein expression and gene amplification, an ECOG performance status of 0 or 1, and adequate organ and cardiac function.
Receipt of certain prior therapies are grounds for exclusion from the study, including; allogeneic stem cell transplant, any anti-CD47 or anti-signal regulatory protein alpha agent, and systemic anticancer therapy within 4 weeks of the study. The existence of a prior of concurrent invasive malignancy that can interfere with the safety/efficacy of study treatment prohibits individuals from enrolling. Further exclusion criteria include untreated brain metastases, leptomeningeal disease, active hepatitis, infection, and other comorbidities.
1. Zymeworks and ALX Oncology announce first patient dosed in phase 1b/2 clinical trial of zanidatamab and evorpacept (ALX148) in patients with advanced HER2-expressing breast cancer and other solid tumors. News release. Zymeworks, Inc. Ocotober 5, 2021. Accessed October 7, 2021. https://bwnews.pr/3DAomb1
2. A study of zanidatamab (ZW25) with ALX148 in patients with advanced her2-expressing cancer. Clinicaltrials.gov. Accessed October 7, 2021. https://bit.ly/3oBOv4S