Evorpacept Combo Shows Higher Response in HER2-Positive Gastric Cancer

Adding evorpacept to trastuzumab, ramucirumab, and paclitaxel produced a higher investigator-assessed objective response rate than the three-drug regimen alone in patients with previously treated, HER2-positive advanced gastric or gastroesophageal junction cancer. The phase 2 findings from the ASPEN-06 trial were published in Nature Medicine.

Evorpacept blocks the interaction between CD47 and signal regulatory protein α, a pathway involved in suppressing phagocytosis. In the multinational, open-label trial sponsored by ALX Oncology, 127 patients whose disease had progressed after HER2-directed treatment were randomly assigned to the evorpacept combination (n = 63) or trastuzumab, ramucirumab, and paclitaxel alone (n = 64). The primary analysis compared objective response rates both between arms and against a prespecified 30% historical benchmark.

Response rates were 40.3% with evorpacept and 26.6% with the control regimen, a 13.7-percentage-point difference that exceeded the prespecified 8-point threshold. Among patients with HER2 positivity confirmed by a fresh biopsy after prior treatment, rates were 54.8% and 23.1%, respectively, exceeding the prespecified between-arm difference. However, neither evorpacept response rate met the trial’s statistical criterion when compared with the historical benchmark.

Median duration of response was 15.7 months with evorpacept versus 7.6 months with the control regimen. Median progression-free survival was 7.5 versus 7.4 months in the full study population. At a later data cutoff, overall survival was similar between arms. Grade 3 or higher treatment-emergent adverse events occurred in 90.5% and 79.4% of treated patients, respectively; neutropenia and anemia were more frequent with evorpacept.

Post hoc analyses suggested greater response among patients with retained HER2 positivity and high tumor CD47 expression. The authors cautioned that the trial was open-label, subgroup sizes were small, and the CD47 cutoff was identified and evaluated in the same dataset. The study did not advance to phase 3 for strategic reasons; the investigators called for prospective confirmation.

Source: 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. Published online September 24, 2026. doi:10.1038/s41591-026-04700-3