<scp>HEBERSaVax</scp> immunotherapy combined with first‐line chemotherapy in advanced ovarian cancer: Phase <scp>II CENTAURO</scp> ‐4 trial results

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-A₁₂₁ 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.