Evorpacept's CD47-biomarker-selected HER2+ mBC strategy tests whether innate immune checkpoint blockade can create durable responses post-ENHERTU

ALX Oncology is a clinical-stage company developing evorpacept, a targeted cancer drug for HER2-positive metastatic breast cancer that has progressed after prior treatment, which is not yet approved.

Evorpacept is a CD47/SIRPα innate immune checkpoint blocker being evaluated in combination with zanidatamab and chemotherapy in heavily pretreated HER2+ metastatic breast cancer patients who have progressed after ENHERTU. The thesis turns on whether the CD47-high biomarker-selected population in ASPEN-Breast Phase 2 reproduces the striking early response data at a scale sufficient to support a registrational path. The primary risk is that ENHERTU's entrenched dominance in HER2+ mBC, with response rates and survival data that have already reset the standard of care, leaves a shrinking and fragmented patient population for any subsequent-line agent.