Evorpacept (CD47 blocker) + TRP lifts ORR in 2L/3L HER2+ gastric/GEJ—PFS flat in ITT

Evorpacept blocks the CD47–SIRPα interaction to enhance macrophage-mediated tumor-cell killing, here combined with trastuzumab + ramucirumab + paclitaxel (TRP). In the randomized Phase II portion of ASPEN-06 (NCT05002127), 127 patients with previously treated HER2-overexpressing advanced gastric/GEJ cancer received evorpacept + TRP or TRP alone. ORR was 40.3% vs 26.6% in the ITT population and 54.8% vs 23.1% in the prespecified fresh-biopsy HER2+ subgroup; these differences exceeded the prespecified between-arm thresholds, although neither cohort met the stricter statistical criterion against the historical 30% ORR benchmark. Median DOR was 15.7 vs 7.6 months, but ITT median PFS was nearly identical at 7.5 vs 7.4 months; in the fresh-biopsy HER2+ subgroup it was 9.0 vs 7.4 months. Hematologic toxicity was more frequent with evorpacept. Importantly, T-DXd is now a recommended second-line option for HER2+ gastric/GEJ cancer, with repeat HER2 testing after progression recommended to confirm retained HER2 expression.