ALX Oncology's evorpacept hits 63.6% ORR in HER2+ gastric subgroup
ALX Oncology has published Phase 2 data from its ASPEN-06 trial in Nature Medicine, reporting that its CD47-blocker evorpacept, combined with trastuzumab, ramucirumab and paclitaxel, achieved a 40.3% objective response rate (ORR) in previously treated HER2-positive gastric and gastroesophageal junction cancer, against 26.6% for the chemotherapy backbone alone.
The headline figures, while encouraging, become substantially more striking in a post-hoc biomarker subgroup. Among patients whose tumours retained HER2 positivity and showed elevated CD47 expression, defined as at least 5% CD47 IHC3+ staining, the evorpacept arm recorded a 63.6% ORR against 23.1% for controls. Median progression-free survival in that subgroup extended to 19.5 months versus 7.0 months, and median duration of response reached 25.5 months compared with 8.4 months. The 127-patient Phase 2 portion of ASPEN-06 was a randomised, open-label, international, multicentre study (NCT05002127).
Biomarker strategy takes centre stage
Chief medical officer Barbara Klencke said the results support the company's hypothesis that both retained HER2 expression and elevated CD47 levels drive efficacy through enhanced antibody-dependent cellular phagocytosis, and that CD47 expression is shaping up as a meaningful predictive biomarker for patient selection. "These findings further strengthen our conviction in the ongoing Phase 2 ASPEN-09-Breast clinical trial," she added.
That conviction comes with a notable strategic caveat. ALX Oncology has elected not to pursue a US registrational Phase 3 programme in gastric cancer, citing resource allocation priorities, and will instead seek a development partnership to advance evorpacept in that indication. The company is directing internal investment toward ASPEN-09-Breast, which is evaluating evorpacept in combination with trastuzumab and chemotherapy in HER2-positive metastatic breast cancer, with topline data from 80 patients expected in mid-2027.
Market and competitive context
The CD47 "don't-eat-me" signal has attracted considerable industry attention as an innate immune checkpoint, but the field has had mixed fortunes. Several earlier CD47-targeting programmes encountered tolerability challenges or failed to demonstrate convincing efficacy in unselected populations, prompting a broader shift toward biomarker-stratified designs, the same approach ALX is now leaning into. Publication in Nature Medicine lends the dataset a degree of peer-reviewed credibility that conference abstracts lack, though the post-hoc nature of the most impressive subgroup findings means regulators and investors will weigh them carefully.
HER2-positive gastric and gastroesophageal junction cancer remains a difficult-to-treat setting. The combination of trastuzumab-based therapy with novel immuno-oncology agents is an active research direction, with a number of academic and industry groups exploring antibody combinations. ALX's pivot to breast cancer reflects both the unmet need in that indication and the stronger commercial dynamics of HER2-positive metastatic breast cancer relative to second- or third-line gastric.
The mid-2027 readout from ASPEN-09-Breast will be the defining near-term catalyst for ALX Oncology. Whether the biomarker-selection hypothesis holds in a different tumour type will be closely watched by investors who have followed evorpacept through multiple indication cycles. ALX also has a second candidate, ALX2004, an EGFR-targeted antibody-drug conjugate in Phase 1 dose escalation, though that programme remains early stage.