Abstract 5185
Background
Expression of hyaluronidase from the selective oncolytic adenovirus VCN-01 modifies tumor matrix in pancreatic tumours. Such effect enhances gemcitabine uptake and induces potent immunomodulatory signals that could help recruit CD8+-T cells.
Methods
VCN-01 was administered as a single IV injection to 40 patients with ECOG 0-1 at doses ranging from 1E11 to 1E13 viral particles per patient (vp) as a single agent in patients with advanced solid tumors or in combination with gemcitabine/nab-paclitaxel in patients with advanced pancreatic adenocarcinoma using two independent administration regimens (concomitant or sequential). Blood levels of VCN-01 DNA and hyaluronidase together with several immunological markers and VCN-01 presence in paired tumor biopsies were measured. Response was assessed using RECIST v1.1 criteria.
Results
The most commonly reported VCN-01-associated adverse events of grade 3 or higher included transaminase increase, thrombocytopenia and neutropenia, accounting for 27% and 10% of patients respectively for the combination of VCN-01 with gemcitabine/nab-paclitaxel in the concomitant and the sequential regimen. Recommended Phase 2 Dose (RP2D) was 1E+13vp/patient both in monotherapy and in combination with chemotherapy in a sequential regimen whereas 3.3E+12vp was the RP2D for the concomitant regimen. VCN-01 reached and replicated in tumors when administered systemically. VCN-01 dose correlated with hyaluronidase positivity in sera and sustained viremia for over 3 weeks indicating replication. VCN-01 administration changed tumour environment into a more pro-inflammatory state, inducing CD8 T-cells infiltration and upregulation of IDO in 64% patients. RECIST evaluation resulted in a response rate between 40-45% ORR depending on regimen including a complete response and several partial responses.
Conclusions
VCN-01 shows a good safety profile when administered systemically in combination with the standard of care for pancreatic cancer. Its ability to reach systemically the tumours and modify tumour matrix to favour immune infiltration results in evidences of clinical activity.
Clinical trial identification
2012-005555-16.
Editorial acknowledgement
Legal entity responsible for the study
VCN Biosciences.
Funding
VCN Biosciences.
Disclosure
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, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pharma Mar; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): ARMO Biosciences; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Boston Medicals; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): VCN Biosciences. M. Gil Martín: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: PharmaMar; Speaker Bureau / Expert testimony: AstraZeneca. R. Alvarez Gallego: Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Shire. T. Macarulla Mercade: Advisory / Consultancy: Servier; Advisory / Consultancy: Shire; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Baxter; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Aslan; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Halozyme; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Merimarck; Research grant / Funding (institution): Millenium; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pharmacyclics. M.C. Riesco Martinez: Speaker Bureau / Expert testimony: Merck. C. Guillen-Ponce: Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): PH Research; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Erytech Pharma; Research grant / Funding (institution): VCN Biosciences; Research grant / Funding (institution): Halozyme. N. Vidal: Research grant / Funding (institution): VCN Biosciences. F.X. Real: Speaker Bureau / Expert testimony: Roche; Research grant / Funding (institution): VCN Biosciences. V. Maliandi: Full / Part-time employment: VCN Biosciences. A. Mato-Berciano: Full / Part-time employment: VCN Biosciences. M. Bazan-Peregrino: Full / Part-time employment: VCN Biosciences. 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. 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. Salazar: Advisory / Consultancy, Research grant / Funding (institution): VCN Biosciences; Advisory / Consultancy: Agendia; Advisory / Consultancy: Guardiant 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 Pharma; 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. All other authors have declared no conflicts of interest.
Resources from the same session
3905 - Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer
Presenter: Krittiya Korphaisarn
Session: Poster Display session 2
Resources:
Abstract
3963 - Robot-assisted natural orifice specimen extraction surgery for radical resection of colorectal cancer
Presenter: Zhengchuan Niu
Session: Poster Display session 2
Resources:
Abstract
3989 - Bevacizumab as adjuvant treatment for colon cancer: Updated results from the AVANT phase III Study by the GERCOR Group
Presenter: Thierry André
Session: Poster Display session 2
Resources:
Abstract
4741 - Real world data on adjuvant chemotherapy for high-risk stage II colorectal cancer – the role of tumor side
Presenter: Camila Araujo de Carvalho
Session: Poster Display session 2
Resources:
Abstract
4973 - Oncological Outcome and Safety of Bevacizumab (BV) Therapy in Patients with Occlusive Colon Cancer and Self-Expandable Metal Stents (SEMS)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 2
Resources:
Abstract
2295 - Active chronic hepatitis B increases the risk of liver metastasis of colorectal cancer- a retrospective clinical study of 7187 consecutive cases of newly diagnosed colorectal cancer
Presenter: Lei Zhao
Session: Poster Display session 2
Resources:
Abstract
3845 - Comprehensive Evaluation of Recurrence Risk (CERR) Score for Colorectal Liver Metastases: Development and Validation
Presenter: Wei Ye
Session: Poster Display session 2
Resources:
Abstract
1976 - BRAF-mutated colorectal metastases: what is the benefit of liver surgery? Results from a cohort of 91 patients.
Presenter: Sahir Javed
Session: Poster Display session 2
Resources:
Abstract
2688 - The smallest colorectal liver metastasis size as a prognosis factor after laparoscopic liver resection
Presenter: Baptiste Cervantes
Session: Poster Display session 2
Resources:
Abstract
4961 - Validation of GAME score risk groups in resected colorectal cancer liver metastases and the prognostic relevance of KRAS, NRAS and BRAF mutation analysis
Presenter: Berta Martin-Cullell
Session: Poster Display session 2
Resources:
Abstract