Agenus has reported results from a Phase II trial, evaluating the combination of botensilimab (BOT), balstilimab (BAL), and agenT-797 alongside ramucirumab and paclitaxel, in advanced programmed cell death protein 1 (PD-1) refractory gastroesophageal adenocarcinoma patients.
The trial results mark the first assessment of this regimen in patients who experienced disease progression after first-line treatment.
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It focused on immune priming and treatment sequencing.
In this investigator-initiated study, patients received induction with agenT-797 (alone or with BOT/BAL), followed by the complete combination or initiated the combination without induction. Longitudinal biomarker samples were taken throughout.
Among 17 patients, the regimen delivered a disease control rate (DCR) of 77%, with a subset experiencing long-term survival over 20 months.
The induction arm reported a median progression-free survival (PFS) of 6.9 months, compared with 3.5 months for the non-induction arm, and a median overall survival (OS) of 9.5 versus 5.2 months.
Furthermore, the data revealed that 43% of induction-treated patients were alive at both 12 and 18 months.
Agenus research vice-president Dhan Chand said: “These findings illustrate the mechanistic synergy of agenT-797 with botensilimab and balstilimab in this PD-1 refractory setting.
“The induction approach promoted significant intratumoral infiltration of T cells and dendritic cells, the formation of organised tertiary lymphoid structures in on-treatment biopsy tissue from a patient with durable benefit, and activation of peripheral CD4 and CD8 T-cell populations.
“These changes are consistent with immune priming and tumour immune reprogramming, providing a biological rationale for the improved progression-free survival observed with the induction strategy.”
The study failed to reach its primary endpoint of objective response rate, but durable disease control and survival outcomes suggest further study is warranted.
Safety profiles aligned with component treatments. The most prevalent adverse events were anorexia, diarrhoea, fatigue, fever, nausea, and mucositis, alongside immune-related events such as colitis, dermatitis, enteritis, gastritis, hepatitis, and hypothyroidism.
Ongoing analyses are expected to further clarify immune mechanisms, optimal sequencing, and biomarker guidance.
Earlier this month, Agenus enrolled the first patient in the BATTMAN Phase III trial, assessing BOT plus BAL in refractory, unresectable microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC).
