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
3536 - Palbociclib plus an aromatase inhibitor as first-line therapy for metastatic breast cancer in US clinical practices: Real-world progression-free survival analysis
Presenter: Mylin Torres
Session: Poster Display session 2
Resources:
Abstract
4022 - Ribociclib (RIB) plus letrozole (LET) in male patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) from the CompLEEment-1 trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
3599 - Comparative effectiveness of palbociclib plus letrozole vs letrozole for metastatic breast cancer in US real-world clinical practices
Presenter: Rachel Layman
Session: Poster Display session 2
Resources:
Abstract
901 - Pharmacokinetics (PK), safety, and efficacy of [fam-] trastuzumab deruxtecan with OATP1B/CYP3A inhibitors in subjects with HER2-expressing advanced solid tumors
Presenter: Yung-Jue Bang
Session: Poster Display session 2
Resources:
Abstract
2777 - A Phase 2 study of abemaciclib in patients (pts) with brain metastases (BM) secondary to non-small cell lung cancer (NSCLC) or melanoma (MEL).
Presenter: Solmaz Sahebjam
Session: Poster Display session 2
Resources:
Abstract
3980 - Ribociclib (RIB) + letrozole (LET) in patients (pts) with visceral metastases (VM) or bone-only metastases (BOM) in hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Subgroup analysis from the CompLEEment-1 trial
Presenter: Michelino De Laurentiis
Session: Poster Display session 2
Resources:
Abstract
4024 - Ribociclib (RIB) + letrozole (LET) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) and central nervous system (CNS) metastases: Subgroup analysis from the phase 3b CompLEEment-1 trial
Presenter: Paul Cottu
Session: Poster Display session 2
Resources:
Abstract
2151 - Clinical outcome and toxicity data in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy in a real-world clinical setting.
Presenter: Elena Fountzilas
Session: Poster Display session 2
Resources:
Abstract
3994 - Safety and efficacy of Ribociclib (RIBO) + letrozole (LET) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Interim results from the Italian cohort of the CompLEEment-1 (C-1) study.
Presenter: Michele De Laurentiis
Session: Poster Display session 2
Resources:
Abstract
1370 - Interim Results From CompLEEment-1 (A Phase 3b Study of Ribociclib and Letrozole as First-Line Therapy for Advanced Breast Cancer in an Expanded Population): Spanish cohort results
Presenter: Javier Salvador
Session: Poster Display session 2
Resources:
Abstract