A phase 1b study to evaluate the safety, tolerability and preliminary efficacy of a heterologous prime boost vaccination (ATP150/ATP152/ATP162, VSV-GP154) and ezabenlimab (BI 754091) in patients with pancreatic ductal adenocarcinoma.

Abstract

TPS794 Background: Recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) is common, and long-term survival remains low, highlighting the need for new therapies. The KISIMA-02 study explores a heterologous prime boost cancer vaccination platform, consisting of a protein (ATP150, ATP152, or ATP162) and a viral vector vaccine (VSV-GP154), specifically designed to target GI cancers. The protein vaccine contains three elements essential to generate potent antitumoral cellular immunity: a proprietary cell-penetrating peptide for antigen delivery, a proprietary toll-like receptor peptide agonist with self-adjuvant properties, and a tailored multi-antigenic domain. Methods: This open-label, multicenter, Phase 1b study evaluates the safety, tolerability and preliminary efficacy of an ATP150/ATP152/ATP162, VSV-GP154 vaccination in combination with ezabenlimab, a PD-1 inhibitor, in patients with PDAC. Patients are recruited from approximately 30 sites in North America and Europe. The study comprises two main phases: a safety and immunogenicity phase (Parts A and B, 55 patients enrolled) and a randomized efficacy phase (Part C: expected to begin in Q4, 2025). Part A began in July 2023, is now complete and assessed the safety and tolerability of ATP150/ATP152 with VSV-GP154, while Part B, ongoing, aims to evaluate the safety and tolerability, as well as the maximum tolerated dose and/or the recommended Phase 2 Dose of ATP150/ATP152, VSV-GP154 in combination with ezabenlimab. Part C will assess the efficacy and safety of the ATP162 and VSV-GP154 vaccination in combination with ezabenlimab, as well as two ATP162 dosing regimens. The primary endpoint will be disease-free survival, and key secondary endpoints include the proportion of patients with ctDNA clearance or reduction, with normalization of CA19-9 and occurrence of AEs according to CTCAE grading during the on-treatment period. Approximately 85 patients with resected PDAC will be recruited in Part C. After a safety run-in (Part C0), patients will be randomized to receive ATP162, VSV-GP154 and ezabenlimab, or undergo active surveillance. Part C1 will randomize ≈45 patients in a 2:2:1 ratio between two dosing regimens of the cancer vaccine combined with ezabenlimab and active surveillance. Part C2 will randomize ≈35 patients in a 2:1 ratio between the selected dosing regimen of vaccine plus ezabenlimab and active surveillance. Individuals aged ≥18 years; with histologically confirmed PDAC, ECOG performance status of 0–1; macroscopically complete resection following completion of adjuvant, neoadjuvant or perioperative chemotherapy with (m)FOLFORINOX will be eligible. Clinical trial information: (NCT05846516). Oberstein P*, Rasco D*- *equal contribution as first authors. Clinical trial information: NCT05846516 .