New Biomarker May Unlock Treatment for Advanced HER2+ Breast Cancer

SOUTH SAN FRANCISCO, CA – January 30, 2026 – In the relentless fight against advanced breast cancer, a potential new strategy is emerging that could help clinicians select the right treatment for the right patient. ALX Oncology today announced new findings suggesting a protein known as CD47 could be a key predictive biomarker for treating HER2-positive breast cancer, a discovery that may offer a new lifeline to patients who have exhausted other options.

Data from an exploratory analysis of a Phase 1b/2 clinical trial showed that the expression level of CD47 on cancer cells helps predict how well patients with advanced HER2-positive breast cancer respond to the company’s investigational therapy, evorpacept. When combined with Jazz Pharmaceuticals’ ZIIHERA® (zanidatamab-hrii), the treatment demonstrated significant activity, but primarily in patients whose tumors had higher levels of the CD47 protein.

This finding provides a crucial piece of the puzzle for the clinical-stage biotechnology company, potentially refining the path forward for its lead drug candidate.

A Biomarker to Guide the Battle

At the heart of this development is the CD47 protein, often called the “don’t eat me” signal. Many cancer cells display this protein on their surface to evade the immune system, effectively telling macrophages—the immune system's cellular cleanup crew—to leave them alone. Evorpacept is a CD47 inhibitor designed to block this signal, thereby enabling macrophages to recognize and destroy cancer cells.

The new data comes from the NCT05027139 trial, which evaluated the evorpacept-zanidatamab combination in heavily pretreated patients, a group with significant unmet medical need. The initial results, presented at the 2024 San Antonio Breast Cancer Symposium, were already promising. In a small group of nine patients with centrally confirmed HER2-positive disease who had received a median of six prior therapies, the combination achieved a 56% confirmed objective response rate (cORR) and a median progression-free survival (mPFS) of 7.4 months. The latest exploratory analysis adds a critical layer of insight, revealing that these positive responses were largely confined to patients with higher CD47 expression.

“These new findings support a CD47-dependent, HER2-driven biology for evorpacept,” said Barbara Klencke, M.D., Chief Medical Officer at ALX Oncology, in the company's press release. “Going forward, we believe that a biomarker-driven approach incorporating CD47 expression may optimize patient selection for evorpacept combinations with HER2-targeted agents.”

This isn’t the first time ALX Oncology has seen this pattern. The results mirror findings from the ASPEN-06 trial in HER2-positive gastric cancer, where CD47 expression also emerged as a strong predictor of response. In that study, patients with high CD47 levels saw a remarkable 65% response rate and a median duration of response lasting over two years, reinforcing the biomarker’s potential robustness across different cancer types.

Addressing a Critical Unmet Need

The landscape for HER2-positive breast cancer has been transformed by targeted therapies, with drugs like trastuzumab deruxtecan (Enhertu) setting new standards of care. However, a formidable challenge remains: what to do when a patient’s cancer progresses despite these powerful treatments. For patients who are on their third, fourth, or even later lines of therapy, options dwindle and efficacy drops sharply.

Real-world data for the post-Enhertu setting shows a stark reality, with response rates to subsequent therapies often falling into the 15-20% range and progression-free survival hovering around just four to five months. It is in this challenging clinical space that the results from the evorpacept combination appear most striking. The 56% response rate and 7.4-month progression-free survival seen in the trial, which included patients previously treated with Enhertu, represent a potentially significant improvement over the current expectations for this heavily pretreated population.

By identifying a predictive biomarker, ALX Oncology aims to move beyond a one-size-fits-all approach. If patients with high CD47 expression can be identified upfront, they could be directed toward a therapy that is more likely to work for them, sparing them the time and toxicity of ineffective treatments and offering a more concrete basis for hope.

A Strategic Play in a Crowded Field

For ALX Oncology, a clinical-stage company with a market capitalization under $100 million, the biomarker strategy is not just a scientific pursuit but a crucial business imperative. The HER2-positive cancer market is a multi-billion dollar arena dominated by pharmaceutical giants. Competing head-on is a daunting task.

Instead, the company is pursuing a precision oncology strategy. By focusing on a biomarker-defined patient population where evorpacept may have a superior effect, ALX can carve out a specific, high-need niche. This approach could differentiate evorpacept in a crowded market and provide a clearer path to regulatory approval. If the company can prove its drug offers a substantial benefit to patients with high CD47 expression who have few other options, it could secure a vital role in the treatment paradigm.

Analysts note that while the company is still unprofitable and burning through cash—a common scenario for clinical-stage biotechs—positive clinical data is the ultimate currency. The consistent results across both breast and gastric cancer trials strengthen the company's scientific platform and provide a compelling narrative for investors and potential partners.

The Future of Personalized HER2+ Therapy

The journey for evorpacept and its biomarker-driven approach is far from over. The full data from the exploratory analysis has been submitted for presentation at an upcoming scientific conference, where it will face scrutiny from the broader oncology community. The company's ongoing ASPEN-09-Breast Phase 2 trial is designed to further validate this hypothesis, prospectively evaluating the link between CD47 levels and patient outcomes.

Success in these future trials would not only be a win for ALX Oncology but also a victory for the field of personalized medicine. It would underscore the importance of understanding the underlying biology of a patient's tumor to guide treatment decisions. The ultimate goal is to develop a validated companion diagnostic test that can reliably measure CD47 expression, making this targeted approach a practical reality in clinics worldwide.

As the research continues, the identification of CD47 as a potential predictive biomarker represents a significant step forward. It offers a tangible strategy to improve outcomes for some of the most difficult-to-treat HER2-positive cancer patients and reinforces the principle that the future of cancer care lies in tailoring treatment to the individual.