Infinitopes Doses First Patient in Phase I/IIa Trial of Off-the-Shelf Cancer Vaccine ITOP1 for Resectable Esophageal Adenocarcinoma
Key Insights
Infinitopes (search) has dosed the first patient in the VISTA trial evaluating ITOP1, an off-the-shelf therapeutic cancer vaccine, in resectable esophageal and gastro-esophageal junction adenocarcinoma (search).
The randomized, double-blind, placebo-controlled Phase I/IIa study will enroll 60 patients, adding ITOP1 to standard neoadjuvant FLOT chemotherapy (search) plus durvalumab.
ITOP1 was developed using the Precision Immunomics platform, which employs mass spectrometry-based immunopeptidomics to identify naturally presented tumor antigens, including non-canonical targets.
Oxford-based Infinitopes (search) has dosed the first patient in the VISTA trial, a University of Oxford investigator-initiated Phase I/IIa study evaluating ITOP1, an off-the-shelf therapeutic cancer vaccine designed to reduce recurrence in patients with resectable esophageal and gastro-esophageal junction adenocarcinoma (search).
The randomized, double-blind, placebo-controlled trial begins with an eight-patient Phase I safety and immunogenicity lead-in before expanding to a 52-patient Phase IIa cohort. ITOP1 is being added to standard neoadjuvant FLOT chemotherapy (search) plus durvalumab (Imfinzi), with vaccine doses administered both before and after esophagectomy. Initial safety and immunological data are expected in early 2027.
The Unmet Need in Esophageal Adenocarcinoma (search)
Despite advances in perioperative therapy, esophageal adenocarcinoma (search) remains difficult to cure. Real-world five-year survival with FLOT chemotherapy (search) stands at approximately 32%, while pathological complete response rates remain modest. Durvalumab received US FDA approval in 2025 alongside FLOT for resectable gastric and gastro-esophageal junction adenocarcinoma (search) following the MATTERHORN trial, which demonstrated 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.
Precision Immunomics Platform and Vaccine Design
ITOP1 was developed using Infinitopes (search)' Precision Immunomics platform, which applies mass spectrometry-based immunopeptidomics to identify peptides naturally presented on tumour cells rather than relying on computational prediction. The platform also incorporates non-canonical antigens derived from alternative reading frames and non-coding regions, broadening the range of tumour-specific targets. These 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.
Scientific Rationale for Neoadjuvant Vaccination
Interest in neoadjuvant cancer vaccination has grown as evidence suggests treatment is more effective while the primary tumour remains intact. Although esophageal adenocarcinoma (search) 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.
Competitive Landscape
Therapeutic cancer vaccines are being developed across multiple platforms, including personalized mRNA and neoantigen approaches. Transgene's TG4050, developed with NEC Corporation, uses a modified vaccinia Ankara vector to deliver personalized neoantigens in head and neck and ovarian cancers, while Chinese academic groups are evaluating personalized mRNA vaccines in esophageal squamous cell carcinoma, a biologically distinct disease from the adenocarcinoma targeted by ITOP1.
ITOP1 appears to be the only off-the-shelf viral vector vaccine in clinical testing for resectable esophageal or gastro-esophageal junction adenocarcinoma (search) and the only randomized, placebo-controlled study evaluating neoadjuvant vaccination in this setting. Phase IIa results, expected from 2027, should provide an early test of whether a shared-antigen strategy can approach the efficacy of personalized cancer vaccines.
Infinitopes (search), a University of Oxford spinout backed by Cancer Research UK that has raised more than USD 35 million, plans to apply its Precision Immunomics platform across additional solid tumours that remain in antigen discovery.