CD47 Protein May Predict Evorpacept Success in Metastatic Breast Cancer

New data from a phase 1b/2 clinical trial shows that a specific protein called CD47 can help predict how well the investigational drug evorpacept works for patients with metastatic breast cancer, ALX Oncology Holdings Inc. announced in a news release.

The findings, derived from an exploratory analysis of patients with HER2-positive cancer that had spread to other parts of the body, were released by the company to help identify which individuals are most likely to benefit from this combination therapy: By measuring CD47 expression levels, researchers believe they can better select patients for evorpacept when used alongside the targeted treatment Ziihera (zanidatamab-hrii).

Main data that support the findings

The recent exploratory analysis revealed that the anti-tumor activity of evorpacept is closely tied to the level of CD47 expression found in a patient's cancer. In this trial, positive responses were largely restricted to patients with higher levels of CD47 expression. This protein serves as a biomarker, a biological signpost that helps doctors predict whether a patient will respond to the treatment.

These breast cancer findings reinforce previous results from the ASPEN-06 clinical trial. That study demonstrated that CD47 expression is also a predictive biomarker for patients with advanced gastric cancer that has retained HER2 expression.

In the nine patients with centrally confirmed HER2-positive metastatic breast cancer, the combination of evorpacept and Ziihera produced significant clinical results:

• Confirmed objective response rate (cORR): 56% (five out of nine patients)
• Median progression-free survival (mPFS): 7.4 months

These outcomes are particularly notable because the participants were heavily pretreated, having received a median of six prior therapies, including the medication Enhertu (fam-trastuzumab deruxtecan-nxki), before entering the trial.

Trial details

The phase 1b/2 trial is an open-label, multi-center study evaluating the potential of evorpacept combined with Ziihera. The trial included patients with previously treated, inoperable, locally advanced or metastatic HER2-expressing breast cancer and other cancer types.

The primary results of this trial were first presented at the 2024 San Antonio Breast Cancer Symposium (SABCS). Following that presentation, researchers conducted an additional exploratory analysis specifically to identify biomarkers that could explain why patient responses vary.

ALX Oncology is also moving forward with a phase 2 trial called ASPEN-09-Breast. The company stated that the combined data from the current study and the ASPEN-06 trial have increased their confidence in this ongoing larger study. The complete biomarker analysis from the phase 1b/2 trial has been submitted for presentation at an upcoming scientific congress.

Safety

The trial results demonstrated that the combination of evorpacept and Ziihera has a manageable safety profile in patients who have already undergone extensive previous treatments. Maintaining a manageable safety profile is essential for patients whose bodies have already been affected by multiple rounds of earlier therapy.

By using CD47 expression as a biomarker to guide patient selection, researchers hope to optimize the use of the drug. This means the therapy can be directed toward those most likely to experience a durable benefit, potentially avoiding unnecessary treatment for those whose cancer biology may not respond to the combination.

Evorpacept is designed as a foundational therapy for immuno-oncology and is currently being evaluated in several ongoing clinical trials for a wide range of cancer indications. ALX Oncology's second candidate, ALX2004, is also undergoing early-phase testing in patients with solid tumors, as the company continues to advance novel therapies designed to treat cancer and extend patients' lives.

References

1. “New Data Demonstrate CD47 Expression Level Helps Predict Response to ALX Oncology’s Evorpacept in Combination with Ziihera (zanidatamab-hrii) in Advanced HER2-Positive Breast Cancer,” by ALX Oncology Holdings Inc. News release; Feb. 2, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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