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

Bull

A positive outcome would be a confirmed ORR meaningfully above historical salvage-therapy benchmarks (roughly 15-25% in post-ENHERTU HER2+ mBC) in the CD47-high selected subgroup, ideally with early PFS signals consistent with the 20+ month mDOR and 22-month mPFS seen in the Phase 1b zanidatamab combination data. Such a result would validate the CD47 biomarker-selection strategy as a generalizable principle across HER2-directed combinations, create a clear regulatory and partnering path, and differentiate evorpacept as a backbone for post-ENHERTU salvage.

Bear

The most likely failure mode is that the CD47-high biomarker does not enrich sufficiently for response in the broader Phase 2 population — the Phase 1b signal came from only 5 centrally confirmed HER2+/CD47-high patients, and small-sample inflation is a real risk. A second failure mode is that post-ENHERTU tumor biology (HER2 heterogeneity, immune exhaustion depth) blunts phagocytic priming even with CD47 blockade, producing ORRs indistinguishable from standard salvage regimens and invalidating the core mechanistic premise.