Updated data from the Phase 2 ASPEN-06 trial reveals that ALX Oncology's evorpacept, when combined with trastuzumab, ramucirumab, and paclitaxel (ETRP), demonstrates a promising and durable clinical response in patients with previously treated HER2-positive advanced gastric or gastroesophageal junction (GEJ) cancer. The findings, presented at the 2025 ASCO Gastrointestinal Cancers Symposium, suggest evorpacept's potential as a valuable addition to the treatment landscape for this challenging cancer.
The ASPEN-06 trial (NCT05002127) is a randomized, multi-center, international study evaluating evorpacept in combination with trastuzumab, ramucirumab, and paclitaxel (collectively, ETRP) versus trastuzumab, ramucirumab, and paclitaxel (TRP) alone. The study enrolled patients with HER2-positive gastric/GEJ cancer who had previously received an anti-HER2 agent. The primary endpoint was investigator-assessed overall response rate (ORR).
Key Findings from ASPEN-06
The trial's results showed a significant improvement in ORR in the evorpacept arm. In the intent-to-treat (ITT) population, ETRP demonstrated an ORR of 41.3% compared to 26.6% for the TRP control. Notably, in patients with confirmed HER2-positive expression as determined by either fresh biopsy or ctDNA, the addition of evorpacept to TRP resulted in a 48.9% ORR, compared to 24.5% in the TRP control group. The median duration of response (mDOR) in this subgroup was 15.7 months with ETRP versus 9.1 months with TRP alone.
Kohei Shitara, M.D., Director of the Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan, and the study’s presenter, stated, "The updated data from the ASPEN-06 trial highlight the potential clinical utility of CD47 inhibition from evorpacept in combination with trastuzumab, ramucirumab and paclitaxel in patients with previously treated HER2-positive gastric cancer."
Progression-Free Survival and Safety
While overall survival data were not yet mature at the time of data cut, the study also reported on progression-free survival (PFS). In patients with fresh HER2-positive biopsies, ETRP demonstrated a median PFS of 9.5 months compared to 7.1 months in the TRP control group (HR 0.62). In patients with confirmed HER2-positive expression by either fresh biopsy or ctDNA, the PFS Hazard Ratio was 0.64.
Evorpacept plus TRP was generally well tolerated, with the incidence of adverse events in the evorpacept population consistent with those in the TRP control group.
Implications and Future Directions
These findings suggest that evorpacept can enhance the activity of HER2-targeted therapies in patients with HER2-positive gastric cancer. Alan Sandler, M.D., Chief Medical Officer at ALX Oncology, noted, "The results from this trial tell a clear story that when a cancer cell is expressing HER2, evorpacept can combine with a regimen containing an anti-HER2 antibody such as trastuzumab to improve upon the activity you would expect from that regimen alone."
The FDA has granted Fast Track designation to evorpacept for the second-line treatment of patients with HER2-positive gastric or GEJ carcinoma. This designation underscores the unmet need for effective therapies in this patient population and the potential of evorpacept to address this need. ALX Oncology plans to share the updated ASPEN-06 data with the FDA to discuss the path forward for evorpacept as a potential therapeutic option.
