The figure that matters is 17.3 months. That was the median overall survival in the high-dose group of a Phase 1 trial of VCN-01 in head and neck cancer, and the result now sits in the journal Clinical Cancer Research. Theriva Biologics, a clinical-stage company working on cancer treatments, announced the online publication. The paper is titled “Phase I trial of intravenous VCN-01 oncolytic adenovirus and durvalumab in patients with head and neck metastatic squamous cell carcinoma refractory to immunotherapy.”
By the numbers
The trial (NCT03799744) enrolled 20 adults with refractory or metastatic head and neck squamous cell carcinoma whose disease had progressed despite earlier therapy, including anti-PD-(L)1 checkpoint inhibitors. Patients received intravenous VCN-01 before the checkpoint inhibitor durvalumab, at a fixed 1500 mg dose every four weeks, in three groups.
Six patients in Arm I got low-dose VCN-01 (3.3E12 virus particles) four hours before durvalumab. Eight in the sequential Arm II low-dose group got the same dose 14 days ahead. Six more in Arm II high-dose got 1.0E13 virus particles 14 days ahead.
Median overall survival was 10.3 months in Arm I low dose, 15.5 months in Arm II low dose and 17.3 months in Arm II high dose. Median progression-free survival was 1.6, 3.7 and 2.1 months respectively.
What the biopsies showed
Levels of the stroma-degrading enzyme hyaluronidase PH20, expressed when VCN-01 replicates inside a tumour, rose significantly in every patient tested. They peaked around day 3 to 8 for most and stayed detectable until day 28 in 11 of 12 patients. Viral genome levels in blood showed an initial peak right after dosing and a second at day 3 to 8, consistent with the virus replicating in tumours and returning to circulation.
Tumour samples showed higher CD8 and IDO, consistent with more activated cytotoxic T cells moving in, a pattern historically tied to longer survival in this cancer. FoxP3, CD25 and CTLA4 fell, pointing to fewer regulatory T cells and less immune suppression. PD-1 and PD-L1 rose in most patients after VCN-01, and that rise tracked with survival.
Ricard Mesia of the Catalan Institute of Oncology, coordinating investigator, said the trial showed VCN-01 can resensitise tumours in these heavily pretreated patients to durvalumab. He noted that few treatment options exist for immunotherapy-refractory metastatic disease, and said the findings support further development of VCN-01 with checkpoint inhibitors or other immune-modulating therapies.
