Introduction/Background This was an exploratory, multicenter study of VB10.16 immunotherapy in patients with HPV16+ CIN 2/3.
Methodology VB10.16 is a naked DNA plasmid vaccine. It encodes for a recombinant protein consisting of 3 modules: mutation-inactivated HPV16 E7/E6 protein linked to human chemokine MIP-1α via a dimerization module derived from human IgG3. The unique mode of action is that it directly targets APCs, then HPV16+ infected tissue and mediates cell killing.
This study with 34 CIN 2/3 patients was divided into a Dosing Phase (two vaccination schedules, 3 injections) and an Expansion Phase (4 vaccinations) to assess safety/tolerability immunogenicity and preliminary signs of efficacy with VB10.16. Patients were followed for 24 weeks by colposcopy, cytology, HPV16+ testing and histology. Immunological testing were IFN-γ ELISpot, IHC, PD-L1. The median age was 29.0 years, 70.6% had CIN 2, 29.4% had CIN 3, all were HPV16 positive (one patient withdrew as she was HPV16 negative), and 44% positive for other HPV types at inclusion.
Results Treatment with VB10.16 was well tolerated, and mostly injection site related adverse events were reported. No patients experienced SAEs, or discontinued the study vaccine. The highest grade AEs were Grade 3 in 3 patients. IFN-γ ELISpot data from the Dosing Phase identified the superior dose regimen and suggested a further enhancement with adding a fourth dose. All patients in the Expansion Phase elicited a HPV16-specific T-cell response where 94% showed an increased response after vaccination. Signs of efficacy (CIN regression, HPV16+ clearance, lesion size reduction) correlating with immune responses could be observed. In patients without signs of efficacy, an upregulation of PD-L1 was observed which could have inhibited the T-cells response induced by the vaccine.
Conclusion VB10.16 immunotherapy in patients with HPV16+ CIN 2/3 showed promising results. A study for cervical cancer in combination with a checkpoint inhibitor is in Progress.
Disclosure Study was supported by VACCIBODY A.S., Oslo, Norway. Agnete Fredriksen and Mads Axelsen are employees and warrant holders of Vaccibody. Dr. Woelber reports personal fees from Medac Oncology, Tesaro, Roche, Pharmamar, GSK, Jenapharm, Merck, grants from Greiner, outside the submitted work.
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