Dense stroma is a hallmark of hard-to-treat cancers such as pancreatic adenocarcinoma. VCN-01 oncolytic adenovirus is designed to replicate in cancer cells with dysfunctional RB1 pathway, improve tumor targeting and express hyaluronidase to enhance virus intratumor spreading and facilitate drug extravasation into the tumor.
The mechanisms of action of VCN-01 were tested in pancreatic xenograft models after both intravenous and intratumor administration. In a proof of concept phase I clinical trial study (8 patients), VCN-01 was escalated up to 1E+11vp per Endoscopic Ultrasound (EUS)-guided intratumor injection (3x) combined with the standard of care, SoC (gemcitabine or nab-paclitaxel/gemcitabine) in patients with advanced pancreatic adenocarcinoma.
VCN-01 alone showed antitumor efficacy in preclinical models and further increased its efficacy when combined with SoC chemotherapy. VCN-01 replicated within injected tumors regardless of chemotherapy. Hyaluronidase expression by VCN-01 facilitated tumor extravasation and increased uptake of chemotherapy agents and antibodies. Data obtained from a phase 1 clinical trial of VCN-01 administered by repeated intratumor injection showed that the combination treatment was generally well-tolerated although dose limiting toxicity was found at highest dose. When combined with chemotherapy, VCN-01 stabilized the injected lesion in all patients, with a patient showing long progression free survival of 134 weeks. VCN-01 was detected as secondary peaks in blood several days after injection and in tumors at day 20-28, indicating virus replication. Hyaluronidase PH20 presence in sera was confirmed for all patients injected at 1E+11vp. Elastography of VCN-01-treated tumors evidenced reduction in tumor stiffness regardless of nab-paclitaxel co-administration.
VCN-01 replicates and expresses hyaluronidase after intratumor injection both in preclinical models and in patients with pancreatic cancer. Enhanced chemotherapy access and reduction of tumor stiffness favours local control of pancreatic tumours treated with VCN-01 + standard of care.
EudraCT: 2012-005556-42.
VCN Biosciences.
VCN Biosciences.
M. Hidalgo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): EMD; Speaker Bureau / Expert testimony: Ipsem; Speaker Bureau / Expert testimony: Shire; Advisory / Consultancy: SOBI; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Champions Oncology; Advisory / Consultancy: Agenus; Advisory / Consultancy: Erytech; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Pharmacyte; Advisory / Consultancy: Bioline; Advisory / Consultancy, Shareholder / Stockholder / Stock options: BioOncotech; Advisory / Consultancy, Research grant / Funding (institution): Oncomatrix; Advisory / Consultancy: VCN Biosciences; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Nelum; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Eng T Cells. M. Bazan-Peregrino: Full / Part-time employment: VCN Biosciences. B. Laquente: Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Servier; Research grant / Funding (institution): Mylan. R. Alvarez Gallego: Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Shire. A. Mato-Berciano: Full / Part-time employment: VCN Biosciences. M. Giménez-Alejandre: Full / Part-time employment: VCN Biosciences. V. Maliandi: Full / Part-time employment: VCN Biosciences. M.C. Riesco Martinez: Speaker Bureau / Expert testimony: Merck. M. Perez-Carreras: Advisory / Consultancy: Intercept; Research grant / Funding (institution): GENFIT. G. Capella: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: VCN Biosciences. R. Alemany: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: VCN Biosciences; Research grant / Funding (institution): Lokon Pharma; Research grant / Funding (institution): Mologen. R. Salazar: Advisory / Consultancy, Research grant / Funding (institution): VCN Biosciences; Advisory / Consultancy: Agendia; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Roche Diagnostics; Advisory / Consultancy: Ferrer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche Farma; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: AZD; Speaker Bureau / Expert testimony: Celgene; Leadership role, Shareholder / Stockholder / Stock options: Sace MedHealth; Research grant / Funding (institution): PsiOxus; Research grant / Funding (institution): Mologen. E. Blasi: Full / Part-time employment: VCN Biosciences. C. Blasco: Full / Part-time employment: VCN Biosciences. M. Cascallo: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: VCN Biosciences. R. Garcia-Carbonero: Advisory / Consultancy: AAA; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Servier; Research grant / Funding (institution): ARMO; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): VCN Biosciences. All other authors have declared no conflicts of interest.