Trial Design

The VISTA trial is a double-blinded, randomised Phase I/IIa trial for patients with resectable oesophageal adenocarcinoma (OAC) recommended for neoadjuvant chemotherapy. Patients are first screened for HLA types, with only those matching at least one of the specific HLA types would be eligible for the trial.

In the Phase I safety lead-in, the vaccine ITOP1 A/B is administered to the first 8 participants in staggered doses, with the safety assessed by a Data & Safety Monitoring Committee (DSMC). The trial will progress to Phase II unless specific adverse event criteria are met during Phase I, which could result in a safety review.

In Phase II 52 participants will randomly be assigned to receive either ITOP1 or placebo (3:1 ratio). All participants randomised to ITOP1 will receive ITOP1A/B and/or ITOP1C/D and/or ITOP1E/F.  ITOP1 is administered in a prime and boost regimen after neoadjuvant chemotherapy and before adjuvant FLOT chemotherapy.

Doses of ITOP1 depend on the individual participant’s HLA type, ranging from 2.0 x 1010 to a maximum of 6.0 x 1010 viral particles per participant. After 4 cycles of neoadjuvant chemotherapy, participants will receive the first dose of ITOP1 and undergo surgery, followed by a post-surgery recovery period of 8-12 weeks. The boost dose of ITOP1 treatment will be administered 2 weeks prior to the planned initiation of the adjuvant cycles of FLOT. The trial will also monitor for new autoimmune conditions over a 2-year follow-up period. In Phase II, participants will continue treatment and be monitored with imaging and tumour sampling, with an optional long-term follow-up extending up to 3 years after the final visit.