Abstract 5465
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
EudraCT: 2012-005556-42.
Editorial acknowledgement
Legal entity responsible for the study
VCN Biosciences.
Funding
VCN Biosciences.
Disclosure
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.
Resources from the same session
2273 - High performance of serial tumor biopsies in first in human (FIH) phase I trials.
Presenter: Jun Sato
Session: Poster Display session 1
Resources:
Abstract
5933 - Response rates and lesion-level progression patterns of solid tumor patients in an academic phase 1 program: implications for tumor heterogeneity
Presenter: Christopher Chen
Session: Poster Display session 1
Resources:
Abstract
3569 - Clinical Benefit and Response Rate in Early Phase Clinical Trials: First Report from a Single-Institution Study
Presenter: Antonio Marra
Session: Poster Display session 1
Resources:
Abstract
4139 - Patient (pt) selection for immunotherapeutic early-phase clinical trials (ieCTs): a single Phase I Unit experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
4451 - Improving patient selection for immuno-oncology phase 1 trials: an external validation of five prognostic scores at Claudius Regaud Institute of Toulouse, Oncopôle (IUCT-O).
Presenter: Ghassan Al Darazi
Session: Poster Display session 1
Resources:
Abstract
1696 - Demonstrating the Changing Trends in Phase 1 Clinical Trials
Presenter: Christina Guo
Session: Poster Display session 1
Resources:
Abstract
3202 - Participation of Women in phase 1 oncology clinical trials
Presenter: Laura Vidal
Session: Poster Display session 1
Resources:
Abstract
4518 - Predictors for early trial discontinuation of patients with cancer participating in phase I clinical trials
Presenter: Joeri Douma
Session: Poster Display session 1
Resources:
Abstract
4368 - Safety of Tumor Treating Fields delivery to the torso: Meta analysis from TTFields clinical trials
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract