OVM-200, a recombinant overlapping peptide vaccine, breaks immune tolerance to survivin in patients with advanced solid tumours: a multicentre, open-label, dose-expansion, phase 1 study

Survivin (BIRC5) is broadly overexpressed in human cancers but, as a self-antigen, is subject to immune tolerance that limits spontaneous antitumour immunity. OVM-200 is a recombinant overlapping peptide vaccine spanning full-length survivin, with cathepsin S-cleavable linker sequences inserted between adjacent peptides to enhance antigen processing and presentation. OVM-200-100 was a multicentre, open-label phase 1 study conducted at 4 UK sites. The pooled 2,000-μg cohort comprised 27 patients with advanced non-small cell lung, ovarian or prostate cancer, including 24 patients from phase 1b and 3 treated at this dose in phase 1a. OVM-200 was administered subcutaneously every 2 weeks for 3 initial vaccinations, with up to 8 additional doses in patients deriving clinical benefit. The primary endpoint was safety and tolerability, secondary endpoints included survivin-specific immunogenicity, and antitumour activity by RECIST v1.1 was exploratory. OVM-200-related adverse events were exclusively grade 1-2, with no treatment-related grade ≥3 adverse events, dose-limiting toxicities, serious adverse events or deaths. A systematic literature analysis showed low spontaneous anti-survivin seroreactivity in patients with cancer. In our cohort, pretreatment tumours expressed survivin despite low baseline survivin-specific immunity. OVM-200 vaccination subsequently induced robust humoral and cellular responses, with median anti-survivin IgG titres increasing from 20 at baseline to a peak of 81,920 and median interferon-γ ELISpot responses increasing from 16.7 to 504.6 spot-forming units per 10⁶ PBMCs. Patients receiving ≥4 vaccinations developed higher anti-survivin antibody titres and stronger T cell responses than those receiving fewer doses. Among 24 RECIST-evaluable patients, the best overall response was stable disease (SD) in 6 patients (25%). Patients with SD had significantly higher anti-survivin antibody titres than those with progressive disease (PD) (p=0.0418). OVM-200 was well tolerated and induced robust survivin-specific immunity, providing clinical evidence that it can break immune tolerance to self-antigen survivin and supporting further development. ClinicalTrials.gov identifier: NCT05104515 .