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
5345 - Short-term Clinical Outcomes of Robotic-Assisted Total Mesorectal Excision in Rectal Cancer after concurrent chemoradiotherapy
Presenter: Pojung Chen
Session: Poster Display session 2
Resources:
Abstract
5489 - Local immune status in cancer cell nests can be a predictor of survival for rectal cancer with neoadjuvant radiotherapy
Presenter: xijin lin
Session: Poster Display session 2
Resources:
Abstract
1653 - Impact of concomitant medications on disease free survival (DFS) and overall survival (OS) in patients from the PETACC8 study.
Presenter: Clémence Brun
Session: Poster Display session 2
Resources:
Abstract
5206 - Updated results of NORDIC 8, a randomised trial of cetuximab every 2 weeks with FOLFIRI or cetuximab with alternating FOLFIRI/FOLFOX in patients with RAS and BRAF wild type metastatic colorectal cancer.
Presenter: Per Pfeiffer
Session: Poster Display session 2
Resources:
Abstract
2992 - Clinical impact of mucinous and poorly differentiated tumors on the outcome of patients with stage II colon cancer: a TOSCA subgroup analysis
Presenter: Gerardo Rosati
Session: Poster Display session 2
Resources:
Abstract
4753 - Exercise improved adjuvant treatment completion rates and treatment-related toxicities in colorectal cancer: A prospective pilot study
Presenter: Hong Jun Kim
Session: Poster Display session 2
Resources:
Abstract
2735 - Bevacizumab plus Oxaliplatin-Based Chemotherapy as Adjuvant Treatment for Colon Cancer (CC): Updated analysis of stage II disease from the AVANT Phase III Randomized trial by the GERCOR Group
Presenter: Aimery De Gramont
Session: Poster Display session 2
Resources:
Abstract
1843 - Multicenter Validation of the Postoperative Carcinoembryonic Antigen Combined Prognostic Model for Stage Ⅲ Colon Cancer
Presenter: Ji Zhu
Session: Poster Display session 2
Resources:
Abstract
2554 - Impact of the IDEA study on clinical practice for stage III colon cancer patients: a French GERCOR - FFCD - GI UNICANCER national survey.
Presenter: Kaissa Ouali
Session: Poster Display session 2
Resources:
Abstract
3285 - Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer
Presenter: Philip Falk
Session: Poster Display session 2
Resources:
Abstract