ALX Oncology’s ASPEN-06 study showed a 63.6% ORR with evorpacept in HER2-positive gastric cancer with elevated CD47 expression.
Written by: Mayuri Vaja, PharmD
Reviewed By: Pharmacally Editorial Team
ALX Oncology’s investigational CD47 blocker evorpacept produced higher response rates when added to trastuzumab, ramucirumab and paclitaxel in patients with previously treated HER2-positive advanced gastric or gastroesophageal junction (GEJ) cancer. The randomized Phase 2 findings, published in Nature Medicine, also identified tumor CD47 expression as a potential predictive biomarker for treatment benefit.
ASPEN-06 Evaluated Evorpacept After Prior HER2 Therapy
ASPEN-06 (NCT05002127) enrolled patients with metastatic second- or third-line HER2-overexpressing gastric or GEJ adenocarcinoma whose disease had progressed after prior HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy.
The Phase 2 portion enrolled 127 adults and compared evorpacept plus trastuzumab, ramucirumab and paclitaxel (TRP) with TRP alone.
Key ASPEN-06 Findings
- Overall response rate: 40.3% with evorpacept + TRP vs 26.6% with TRP alone
- Retained HER2-positive disease: 48.9% vs 25.0% ORR
- Retained HER2-positive + elevated CD47 expression: 63.6% vs 23.1% ORR
- Median PFS in the high-CD47 subgroup: 19.5 vs 7.0 months
- Median duration of response: 25.5 vs 8.4 months
The 63.6% ORR finding came from a post-hoc biomarker analysis and therefore requires prospective validation.
Retained HER2 and CD47 Represent Separate Biomarkers
The study assessed two distinct biological features.
Retained HER2-positive disease referred to tumors that continued to show HER2 positivity after previous HER2-directed treatment. This status was established using either a fresh tumor biopsy or detection of ERBB2 gene amplification in circulating tumor DNA (ctDNA).
Elevated CD47 expression, by contrast, was assessed separately using immunohistochemistry. The biomarker subgroup was defined as patients with retained HER2-positive disease and at least 5% CD47 IHC3+ staining.
Among this subgroup, evorpacept plus TRP produced an ORR of 63.6%, compared with 23.1% for TRP alone. Median progression-free survival was 19.5 months versus 7.0 months, while median duration of response reached 25.5 months versus 8.4 months.
These findings suggest that both continued HER2 expression and elevated CD47 may contribute to treatment sensitivity, but the predictive value of CD47 remains investigational because the analysis was conducted after the primary study population had been evaluated.
Evorpacept Targets the CD47 Immune-Evasion Pathway
Evorpacept blocks CD47, a protein that can help tumor cells avoid immune-mediated clearance by transmitting a “do not eat me” signal to phagocytic immune cells.
Blocking CD47 may enhance antibody-dependent cellular phagocytosis and potentially increase the activity of antibody-based therapies such as trastuzumab. The ASPEN-06 findings are consistent with this biological rationale, particularly in tumors that retain HER2 expression and have elevated CD47 levels.
The biomarker findings, however, should be distinguished from prospective evidence. Further studies are needed to establish whether CD47 expression can reliably identify patients most likely to benefit from evorpacept.
Development Focus Shifts to Breast Cancer
Despite the activity observed in gastric and GEJ cancer, ALX Oncology has decided not to pursue a U.S. Phase 3 registrational program in gastric cancer. The company said it may explore development partnerships to advance evorpacept in gastric cancer.
The company is continuing the Phase 2 ASPEN-09-Breast trial (NCT07007559), which evaluates evorpacept in combination with trastuzumab and chemotherapy in patients with HER2-positive metastatic breast cancer.
The study is expected to provide topline data from 80 patients in mid-2027.
The ASPEN-06 results therefore provide clinical evidence for continued investigation of evorpacept while also establishing a more specific research question: whether biomarker selection based on retained HER2 status and CD47 expression can identify patients most likely to respond to CD47 blockade combined with HER2-directed therapy.
Reference
ALX Oncology Announces Nature Medicine Publication of ASPEN-06 Phase 2 Clinical Data Demonstrating Strong Responses and Durable Clinical Benefit with Evorpacept in HER2-Positive Gastric Cancer, ALX Oncology, 28 September 2026
Shitara, K., Wainberg, Z., Tabernero, J. et al. Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04700-3
A Study of Evorpacept (ALX148) in Patients with Advanced HER2+ Gastric Cancer (ASPEN-06), ClinicalTrials.gov ID NCT05002127
About the Writer
Mayuri Vaja (Linkedin) is a Pharm.D professional with a strong interest in clinical research, pharmacovigilance, and medical writing, supported by certifications in pharmacovigilance and academic projects exploring AI in healthcare and drug safety.
With a growing focus on evidence-based healthcare and scientific communication, she is developing expertise in clinical research and translating healthcare evidence into clear, meaningful content.
As a Pharmacally healthcare writer, Mayuri is committed to creating accurate, research-driven, and clinically relevant healthcare content while continuously strengthening her professional skills.