ALX Oncology will present updated Phase 2 data from ASPEN-06, indicating that tumor CD47 overexpression may predict response to evorpacept when added to trastuzumab, ramucirumab, and paclitaxel in previously treated HER2-positive gastric/GEJ adenocarcinoma. The randomized Phase 2 portion enrolled 127 patients in the second- or third-line setting after prior HER2-directed and fluoropyrimidine/platinum therapy, with details to be shown in a poster at SITC 2025.
The core development is a shift toward biomarker-defined use of a CD47 blocker in a complex, multi-antibody regimen. Evorpacept, an anti-CD47 agent, is being tested alongside two IgG1 antibodies, trastuzumab and ramucirumab, plus paclitaxel. The company is highlighting CD47 expression as a predictive marker for benefit, a step that, if confirmed with a clear cutoff and reproducible assay, could reshape the Phase 3 plan embedded in this Phase 2/3 trial and focus the program on a biomarker-enriched population.
Strategically, this is an attempt to solve two problems at once: demonstrate additive clinical value on top of an intensive backbone and de-risk the class by prospectively identifying patients most likely to benefit. The CD47 field has struggled with mixed efficacy signals and operational burdens tied to anemia management and combination toxicity. Showing that high CD47 expression aligns with response would let ALX prosecute a tighter, better-powered registrational study, justify the cost and complexity of layering an innate checkpoint inhibitor onto an antibody/chemotherapy regimen, and align with regulators’ increasing preference for prospectively validated, mechanistically coherent biomarkers. It also matches the mechanistic premise for evorpacept: amplifying antibody-dependent cellular phagocytosis from trastuzumab and ramucirumab in HER2-positive disease.
For sites and CROs, a CD47-driven strategy introduces immediate operational implications. Tissue availability and assay logistics become gating factors in a pretreated gastric population where archival biopsies may be limited and fresh tissue can be challenging. Central testing, turnaround times, and cutoffs will drive screen-fail rates and enrollment velocity. If the assay is IHC-based, sites will need standardization and training on pre-analytical variables; if RNA-based, expect longer cycle times and tighter central-lab coordination. For sponsors and vendors, a companion diagnostic partnership, analytical validation package, and global assay harmonization will need to be stood up early to avoid late-stage regulatory friction. Regulators will look for prospectively defined thresholds, bridging data across assay versions, and consistency of effect across geographic regions and prior HER2 therapy exposures, including ADCs where applicable.
The competitive context matters. Second-line gastric cancer increasingly includes antibody-drug conjugates and VEGFR2-based regimens; continuing HER2 targeting beyond progression is not universally standard but can be rational when paired with a macrophage checkpoint inhibitor. Any biomarker-enriched advantage must be clinically meaningful versus contemporary controls and tolerable on top of weekly paclitaxel. Hematologic safety, infusion logistics, and cumulative toxicity management will determine whether this combination can be operationalized outside of select centers.
What to watch next is whether the SITC poster provides magnitude and durability of benefit in CD47-high versus CD47-low cohorts, the assay methodology and prespecified cutoff, and how these data will be folded into the blinded Phase 3 portion. Clarity on whether enrichment or stratification will be used, the status of a co-diagnostic partner, and any adjustments to sample size and geographies will signal the registrational path. If the predictive signal is strong and operationalizable, expect a narrower, faster Phase 3 with tighter biomarker control; if the signal is modest or assay-dependent, the program risks lengthier development and payer scrutiny post-approval.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
