Evorpacept combination increases response rates but misses statistical criterion in gastric cancer trial

The phase 2 portion of ASPEN-06 enrolled 127 patients with pretreated, HER2-overexpressing advanced gastric or gastroesophageal junction cancer. The multicenter, open-label trial randomized patients to evorpacept plus trastuzumab, ramucirumab and paclitaxel (n = 63) or the three-drug regimen alone (n = 64). Evorpacept blocks CD47–signal regulatory protein α signaling to enhance antibody-dependent cellular phagocytosis. The primary endpoint was investigator-assessed objective response rate (ORR).

ORR was 40.3% with evorpacept versus 26.6% with the comparator in the intention-to-treat population. In patients with HER2 positivity confirmed on a fresh post-trastuzumab biopsy, reported ORRs were 54.8% versus 23.1%. Differences of 13.7 and 31.7 percentage points exceeded the respective prespecified thresholds, meeting one of two primary objectives. However, comparisons with the historical 30% response benchmark did not meet the prespecified one-sided significance threshold of 0.025: P = 0.0949 overall and P = 0.030 in the fresh-biopsy subgroup.

Hematologic toxicities were more common with evorpacept, although overall safety was described as similar. These phase 2 findings suggest response activity but do not establish a survival benefit; survival outcomes and detailed adverse-event rates were not provided in the supplied abstract. Interpretation should account for the open-label design, small biomarker subgroup and failure to meet the historical-benchmark statistical criterion.