ALX Oncology Presents P-I/II Trial Data on Evorpacept Combination in Metastatic Breast Cancer (mBC) at ESMO Breast Cancer’26

Why It Matters

The data suggest evorpacept plus Ziihera can deliver durable responses after standard HER2‑targeted therapy, and CD47 expression may serve as a predictive biomarker, shaping future treatment algorithms for refractory HER2‑positive breast cancer.

Key Takeaways

• Evorpacept + Ziihera achieved 33% overall response in 24 HER2+ mBC patients
• HER2‑positive subgroup reached 60% response and 8.3‑month median PFS
• High CD47 expression yielded 100% response and 22‑month median PFS
• Low CD47 expression showed 25% response, underscoring biomarker relevance
• Patients previously treated with Enhertu still responded to the combination

Pulse Analysis

The HER2‑positive metastatic breast cancer market remains fiercely competitive, with trastuzumab deruxtecan (Enhertu) now a standard line of therapy. Yet a sizable fraction of patients progress despite this agent, creating an unmet need for novel mechanisms of action. Evorpacept, a CD47‑blocking antibody, pairs with Ziihera (zanidatamab), a bispecific HER2‑targeted construct, aiming to synergize innate immune activation with precise tumor targeting. This combination reflects a broader industry shift toward immuno‑oncology hybrids that can overcome resistance pathways.

In ALX Oncology's Phase Ib/II exploratory cohort, 24 patients received evorpacept at 20 mg/kg or 30 mg/kg alongside Ziihera. The overall cORR of 33% and mPFS of 3.6 months are modest, but sub‑analyses reveal striking efficacy signals. HER2‑positive patients achieved a 60% response rate and an 8.3‑month mPFS, while those expressing high levels of CD47 reached a 100% response, with median PFS extending beyond 22 months. These findings position CD47 expression as a potential predictive biomarker, echoing similar trends seen with other checkpoint‑modulating agents.

If validated in larger trials, the evorpacept‑Ziihera duo could reshape treatment sequencing after Enhertu failure, offering clinicians a biologically rational option that leverages both adaptive and innate immunity. The data also raise strategic considerations for investors, as ALX Oncology may attract partnership interest from larger oncology players seeking to bolster their CD47 pipelines. Moreover, regulatory pathways for antibody‑drug combinations are becoming clearer, potentially accelerating market entry for a therapy that addresses a high‑unmet‑need segment of HER2‑positive breast cancer patients.