Phase Ib evaluation of a recombinant overlapping peptide survivin immunotherapy: Safety, immunogenicity, and immune–clinical associations in advanced solid tumours.

2651 Background: Survivin (BIRC5) is a tumour-associated self-antigen broadly expressed in solid malignancies but subject to immune tolerance, limiting its value as an immunotherapy target. OVM-200 is a recombinant overlapping peptide (ROP) survivin immunotherapy designed to enhance antigen processing and presentation through both MHC class I and II pathways, thereby overcoming HLA restriction. A Phase Ia study established safety and the recommended regimen. Here we report novel Phase Ib data evaluating extended immunisation and immune–clinical associations. Methods: Phase Ib enrolled a total of 24 patients with advanced NSCLC, ovarian, or prostate cancer who had progressed on standard therapies. Patients received OVM-200 at the recommended regimen (2 mg) with extended immunisation schedules (3–11 immunisations). The primary endpoint was safety and the secondary endpoint was immunogenicity. Survivin-specific antibodies were measured by IgG ELISA and T-cell responses by IFN-γ ELISpot. Tumour response was assessed using RECIST 1.1, with best overall response (BOR) classified as stable disease (SD) or progressive disease (PD). Immune responses were analysed longitudinally and in relation to BOR. Results: The primary endpoint of safety was met, with OVM-200 well tolerated and no dose-limiting toxicities or treatment-related serious adverse events. Survivin expression was detected in tumour tissue in 17 patients prior to immunisation; however, baseline survivin-specific antibody and T-cell responses were low or undetectable, consistent with immune tolerance. The secondary endpoint of immunogenicity was achieved. Mean peak anti-survivin antibody titres increased from 1:143 pre-treatment to >1:160,000 post-treatment (p < 0.001), and mean peak T-cell responses increased from 211 to 859 net SFU/10⁶ PBMCs (p < 0.00001). Antibody responses were durable, rising through Days 113–169, whereas T-cell responses peaked at Day 57 and remained significantly above baseline. Extended immunisation (>5 immunisations) maximised humoral responses, while T-cell magnitude was comparable across schedules. Patients with BOR of SD showed higher and more sustained survivin-specific humoral and cellular immune responses than those with PD. Conclusions: Phase Ib results demonstrate that OVM-200 is safe and immunogenic, achieving both the primary safety and secondary immunogenicity endpoints. OVM-200 overcomes immune tolerance to survivin and induces durable humoral and cellular immune responses. The observed association between stronger immune responses and BOR of SD supports further clinical evaluation and rational combination strategies. Clinical trial information: NCT05104515 .