In this investigator-initiated Phase II trial at Memorial Sloan Kettering Cancer Center, 17 patients with PD-1 refractory gastroesophageal adenocarcinoma received an induction cycle of agenT-797 alone or combined with botensilimab and balstilimab, followed by a full regimen including ramucirumab and paclitaxel. The study compared outcomes between induction and non-induction arms alongside longitudinal biomarker analyses to assess immune priming and sequencing.

The trial achieved a 77% disease control rate across all patients. Those receiving the induction strategy saw median progression-free survival of 6.9 versus 3.5 months (HR 0.19; p=0.015) and median overall survival of 9.5 versus 5.2 months, with 43% of induction-treated patients alive at both 12 and 18 months compared with 20% and 0% in the non-induction cohort.

Correlative analyses revealed significant intratumoral T-cell and dendritic cell infiltration and formation of organized tertiary lymphoid structures in on-treatment biopsies, alongside peripheral activation of CD4 and CD8 T cells. These findings support agenT-797’s role in re-engaging anti-tumor immunity and remodeling the tumor microenvironment in resistant disease.

Safety was consistent with component agents, with fatigue, fever, diarrhea and other manageable adverse events observed. Ongoing analysis of the full biospecimen dataset will inform optimal sequencing strategies and potential biomarkers to guide patient selection and the design of future pivotal trials.