Oxford-based Infinitopes has dosed the first patient in a trial testing whether its off-the-shelf therapeutic cancer vaccine, ITOP1, can reduce recurrence when given before surgery in resectable esophageal cancer, the company announced.
ITOP1 is being evaluated in VISTA, a University of Oxford investigator-initiated Phase I/IIa trial in patients with newly diagnosed, resectable esophageal and gastro-esophageal junction adenocarcinoma. The randomized, double-blind, placebo-controlled study begins with an eight-patient Phase I safety and immunogenicity lead-in before expanding to a 52-patient Phase IIa cohort.
The vaccine is being added to standard neoadjuvant FLOT chemotherapy plus durvalumab (Imfinzi), with doses administered before and after esophagectomy. Initial safety and immunological data are expected in early 2027.
Despite advances in perioperative therapy, esophageal adenocarcinoma remains difficult to cure. Real-world five-year survival with FLOT is about 32%, while pathological complete response rates remain modest. Durvalumab was approved by the US FDA in 2025 alongside FLOT for resectable gastric and gastro-esophageal junction adenocarcinoma after the MATTERHORN trial showed a 29% reduction in the risk of progression, recurrence, or death. ITOP1 aims to further reduce relapse by expanding anti-tumour immune responses before surgery.
The vaccine was developed using Infinitopes' Precision Immunomics platform, which applies mass spectrometry-based immunopeptidomics to identify peptides naturally presented on tumour cells rather than relying on computational prediction. It also incorporates non-canonical antigens derived from alternative reading frames and non-coding regions, broadening the range of tumour-specific targets. The antigens are delivered by an engineered viral vector that drives both MHC class I and II presentation, activating cytotoxic and helper T cells while providing its own immune stimulation.
Interest in neoadjuvant cancer vaccination has grown as evidence suggests treatment is more effective while the primary tumour remains intact. Although esophageal adenocarcinoma is considered immunologically "cold," tumour antigen-specific T cells have been detected in patients, suggesting the immune system can recognize these tumours if sufficiently stimulated.