Abstract 1231P
Background
VCN-01 is an oncolytic adenovirus designed to replicate selectively in cancer cells. It expresses a matrix remodeling-enzyme hyaluronidase and increases immune check-point antibody uptake in preclinical models. It also induces a pro-inflammatory tumor environment after intravenous [i.v] administration in pancreatic cancer patients (pts). VCN-01 may help to overcome previous resistance to anti-PD(L)-1 therapies in pts with R/M HNSCC.
Methods
Phase I dose-escalation study testing two dose levels of i.v. VCN-01 (3,3E12 & 1E13 viral particles, [vp]) combined with a fixed dose of Durvalumab (1500 mg) using 3+3 design in R/M HNSCC pts previously treated with antiPD(L)-1 agents. Two treatment schedules were explored: concomitant (single dose VCN-01 and Durvalumab on day 1, CS), and sequential (single dose of VCN-01 on day -14 and Durvalumab on day 1; SS), both followed by Durvalumab q4 weeks until progression or intolerable toxicity. Fresh tumor biopsies were taken at baseline, post-VCN-01 and post-Durvalumab.
Results
Twenty patients were enrolled: 6 patients in the CS and 14 in the SS. Two DLT occurred in the first dose level of CS (Hepatic Function Abnormal and ALT increased). Only one DLT was reported in SS at 3.3E12 vp. (Guillain-Barre syndrome). Most common treatment-related adverse event (TRAE) (all grades) were pyrexia/influenza like illness in CS (92.8%) and in SS (83.3%). Most frequent G3 VCN-01-TRAEs were pyrexia/ influenza like illness (14.2%) in SS and transaminitis (33%) in CS, all reversible. No G≥4 TRAEs. Sustained blood levels of VCN-01 genomes, hyaluronidase positivity in serum maintained over 6 weeks and increase in CD8 T-cells and upregulation of PD-L1 in tumor were found. Transcriptomic analysis of serial tumor biopsies revealed differential gene expression profiles and downregulation of matrix related pathways after VCN-01 administration. Efficacy evaluation is ongoing.
Conclusions
Treatment with VCN-01 is feasible with an acceptable safety profile when administered with Durvalumab in SS. Based on PK/PD and toxicity, VCN-01 RP2D is 1E13vp. Encouraging biological activity is observed in R/M HNSCC pts.
Clinical trial identification
NCT03799744.
Editorial acknowledgement
Legal entity responsible for the study
Institut Català d’Oncologia (ICO).
Funding
VCN Biosciences.
Disclosure
M. Jove: Financial Interests, Personal, Invited Speaker, Educational: AstraZeneca, Roche; Other, Other, Travel, accomodation and expenses: Takeda, Roche, MSD, VCN. I. Brana: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingellheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, Pharmamar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. M. Oliva Bernal: Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS, MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Other, Teaching activities: MSD, Merck; Financial Interests, Personal, Other, IDMC: Transgene; Financial Interests, Personal and Institutional, Funding: Roche; Financial Interests, Institutional, Invited Speaker: ALX Oncology, MSD, ISA Therapeutics BV, Roche, Ayala Therapeutics, AbbVie, Bayer, boehringer ingelheim, Merck, Debiopharm; Non-Financial Interests, Institutional, Product Samples: Roche. A. Hernando-Calvo: Other, Other, Award: Novartis. C. Erasun Lecuona: Financial Interests, Personal, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Pierre Fabre. M. Bazan Peregrino: Financial Interests, Personal, Full or part-time Employment: VCN Biosciences. A. Mato-Berciano: Financial Interests, Personal, Full or part-time Employment: VCN Biosciences; Financial Interests, Personal, Ownership Interest: Synthetic Biologics. M.V. Maliandi: Financial Interests, Full or part-time Employment: VCN Biosciences; Financial Interests, Stocks/Shares: Synthetic Biologics. F.X. Real: Financial Interests, Research Grant: VCN biosciences, Janssen. R. Alemany: Financial Interests, Research Grant: VCN Biosciences; Financial Interests, Advisory Role: VCN Biosciences; Financial Interests, Stocks/Shares: Synthetic Biologics. G. Capella: Financial Interests, Advisory Role: VCN Biosciences; Financial Interests, Stocks/Shares: Synthetic Biologics. E. Blasi: Financial Interests, Full or part-time Employment: PharmaMar, VCN Biosciences. C. Blasco: Financial Interests, Full or part-time Employment: VCN Biosciences; Financial Interests, Ownership Interest: Synthetic Biologics. M. Cascallo Piqueras: Financial Interests, Member of the Board of Directors: VCN Biosciences; Financial Interests, Stocks/Shares: Synthetic Biologics. R. Mesia Nin: Financial Interests, Personal, Advisory Board: Merck, MSD, BMS, Bayer, Seattle Genetics, Nanobiotix, Boehringer; Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Non-Financial Interests, Principal Investigator, Clinical Trial PI: BMS; Non-Financial Interests, Principal Investigator, Observational trial PI: Merck. All other authors have declared no conflicts of interest.