Abstract:
VEGF‐driven angiogenesis fuels epithelial ovarian cancer progression, ascites, and poor prognosis. Current anti‐VEGF/chemotherapy combinations provide only transient benefits with notable toxicity. HEBERSaVax, a first‐in‐class VEGF‐targeting immunotherapy, combines recombinant VEGF‐A
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with proprietary adjuvants to generate dual anti‐tumor effects: (1) neutralizing VEGF signaling via antibodies and (2) eliminating VEGF‐producing cells through cytotoxic T‐cell responses. We present results from the multicenter, open‐label CENTAURO 4 phase 2 trial evaluating two formulations of HEBERSaVax combined with carboplatin/paclitaxel in advanced epithelial ovarian cancer patients (unresectable or suboptimal debulked). Forty patients were randomized 1:1 to receive either: Group 1: Standard chemotherapy (carboplatin/paclitaxel) plus CIGB‐247 vaccine (800 μg antigen with 200 μg VSSP adjuvant) Group 2: The same chemotherapy regimen plus CIGB‐247 (800 μg antigen with 0.7 mg aluminum phosphate adjuvant). The primary endpoint was progression‐free survival. Secondary endpoints included objective response rate, overall survival, safety, and immune response results. HEBERSaVax exhibited excellent safety profiles and comparable immunogenicity with both adjuvant formulations. Vaccination‐related adverse events were limited to grade 1–2 toxicities. Long‐term outcomes showed promising clinical activity, with a median progression‐free survival of 18 months and a global median overall survival of 32.82 months at 6‐year follow‐up. No statistically significant differences emerged between the VSSP and aluminum phosphate adjuvant formulations for either safety or efficacy endpoints. These clinical outcomes and the vaccine's favorable toxicity profile position HEBERSaVax as a promising immunotherapeutic strategy for improving epithelial ovarian cancer management.