Survivin recombinant overlapping peptide (ROP) vaccine in advanced solid tumours: a first-in-human, multicentre, open-label, phase 1a dose-escalation study.

Background: Survivin, an inhibitor of apoptosis protein (IAP), is highly expressed in various cancers but has weak immunogenicity as a self-derived tumour-associated antigen (TAA). OVM-200, a survivin recombinant overlapping peptide (ROP) vaccine, consists of overlapping peptides linked by the target sequence (LRMK) for cathepsin S, preserving T-cell and most antibody epitopes. OVM-200 elicits both cellular and humoral immune responses against survivin-expressing cancer cells. This phase 1a, multicentre, open-label trial (OVM-200-100) evaluates OVM-200 as a therapeutic vaccine in patients with non-small cell lung, ovarian, and prostate cancer. This Phase 1 trial is also the first time the ROP technology platform has been used in human trials. Methods: Twelve eligible patients received three subcutaneous OVM-200 doses at 2-week intervals using a 3 + 3 dose-escalation design. Four dose levels (250, 500, 1000, and 2000 μg) were tested to determine the optimal dose for phase 1b. The primary endpoint was safety and tolerability, while secondary endpoints included immunogenicity (antibody and T-cell response) and tumour response (RECIST criteria). This trial was registered with ClinicalTrials.gov (NCT05104515) and EudraCT (2021-001545-12) and took place from 28/09/2021 to 04/05/2023. Findings: OVM-200 was well tolerated, with no serious adverse drug reactions (ADRs) or dose-limiting toxicities (DLTs). All adverse events were Grade 1 injection site reactions (ISRs). The 2000 μg dose group achieved the highest median anti-survivin IgG titre (1:327,680) at the end of the study (EOS) and a median ELISpot T cell response of 1282 SFU per million cells on day 22. Disease stabilisation (SD) was observed in 6 of 12 patients (50%), including all 3 patients (100%) in the 2000 μg group, some of which were stabilisations of limited duration. Based on these findings, the 2000 μg dose was selected for further evaluation in phase 1b. Interpretation: OVM-200 is well tolerated and induces a robust humoral response, with a considerable cellular response and preliminary evidence of disease stabilisation. Phase 1b is ongoing to further evaluate its safety and efficacy at the selected dose. Funding: Oxford Vacmedix UK Ltd.