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
- 1University of Oxford
Abstract
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-g 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-{gamma} ELISpot responses increasing from 16.7 to 504.6 spot-forming units per 10 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.
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BibTeX
@misc{wan2026ovm200,
title = {{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}},
author = {P. K.-T. Wan and T. Morris and M. Forster and T. Zhang and M. Flynn and F. Chamberlain and M. Tuthill and F. Thistlethwaite and A. Williams and W. Finch and W. Lu and S. Jiang},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.08.26367556},
url = {https://www.medrxiv.org/content/10.64898/2026.11.08.26367556v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - 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
AU - P. K.-T. Wan
AU - T. Morris
AU - M. Forster
AU - T. Zhang
AU - M. Flynn
AU - F. Chamberlain
AU - M. Tuthill
AU - F. Thistlethwaite
AU - A. Williams
AU - W. Finch
AU - W. Lu
AU - S. Jiang
PY - 2026
DA - 2026/11/08
PB - medRxiv
DO - 10.64898/2026.11.08.26367556
UR - https://www.medrxiv.org/content/10.64898/2026.11.08.26367556v1
AB - 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-g 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-{gamma} ELISpot responses increasing from 16.7 to 504.6 spot-forming units per 10 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.
ER -