Theriva? Biologics announced new clinical data from the Phase 1 investigator-sponsored study with the Institut Catala d?Oncologia (ICO) evaluating VCN-01 in combination with durvalumab for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). These data were presented at the European Society for Medical Oncology (ESMO) Congress, held both virtually and in Madrid, Spain from October 20-24, 2023.

The poster (#937P) titled ?Survival Outcomes in Phase I Trial Combining VCN-01 and Durvalumab (MEDI4736) in Subjects with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Previous Immunotherapy Treatment,? was presented by Maria Jové (Hospitalet de Llobregat, Spain). Key Takeaway: VCN-01 combined with durvalumab showed encouraging overall survival (OS) in patients who previously progressed on anti-PD(L)-1 therapy.

Survival: VCN-01 induced upregulation of PD-L1, which correlated with enhanced patient survival. In the concomitant (CS) cohort at the 3.3×1012 viral particles (vp) dose, overall survival (OS) was 10.4 months and progression free survival (PFS) was 1.7 months. In the sequential (SS) cohort at the 3.3×1012vp dose OS was 15.5 months and PFS was 3.7, whereas in the SS cohort at the 1×1013 vp dose OS was 17.3 months and PFS was 2.1 months.

VCN-01 induces changes in the immune status of tumors. VCN-01 combined with durvalumab increased CD8 T cells, a marker of tumor inflammation and the expression of PD(L)-1 in tumors. An increase of PD(L)-1 CPS (8/11 at day 8; 8/10 at day 28) and CD8 T cells (7/11 at day 8; 5/10 at day 28) from baseline were found in tumor biopsies.

VCN-01 alone increased the CPS score of tumor biopsies at day 8 after administration by 62.5% in the sequential arm. VCN-01 induced PD(L)-1 upregulation with enhanced patient survival. A statistical correlation was observed between CPS on day 8 and patient OS (p=0.005).

Pharmacodynamics and shedding of VCN-01. PH20 expression from VCN-01 peaked on day 3-8 and remained elevated in some patients up to day 42. Quantification of VCN-01 genomes in stool demonstrated viral shedding that peaked at day 8. VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment.

This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient?s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to over 80 patients in Phase 1 and investigator-sponsored clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection).