Therapeutic Vaccine p16 – VicOryx

 

Description

The human cyclin-dependent kinase inhibitor p16INK4a is a tumor antigen expressed in various cancers, including lung and breast cancer. In normal cells, p16INK4a is rarely expressed and leads to immediate senescence. In all cancers associated with high risk human papilloma virus (HR-HPV), p16INK4a is constantly expressed as an early consequence of HR-HPV-mediated cell transformation.

About 5% of all cancers are associated with HR-HPV including virtually all cervical cancers, 85-95% of anal and vulvar cancers, 20-40% of vaginal and penile cancers and 30-60% of head and neck cancers. Currently, two prophylactic vaccines are on the market that induce HPV-type specific protective immunity but do not have a therapeutic effect on HPV infections.

In patients with HR-HPV-associated cancers, humoral and cellular immune responses against p16INK4a occur spontaneously. In healthy people, such immune responses have not been observed.

Mode of Action

The observation that p16INK4a expression triggers specific immune reactions in patients is the basis of the vaccination approach with therapeutic vaccine p16 using a synthetic p16INK4a peptide to prevent outgrowth or to destroy HR-HPV-associated cancers.

VicOryx 01 Trial

Clinical development of VicOryx started in Q4/2011. The Phase I/IIa trial to immunize patients with advanced HR-HPV- and p16INK4a- positive cervical, vulvar, vaginal, penile, anal or head & neck cancer using therapeutic vaccine p16 was successfully completed in Q1/2015. This prospective trial was a two part open-label design conducted at single center.

Primary objective of the Phase I part was safety. Secondary objectives were immune response against therapeutic vaccine p16 and tumor response.

Primary objective of the Phase IIa part was immune response against therapeutic vaccine p16. Secondary objectives were safety and tumor response.

Results: The vaccine was safe, showed strong immune responses against p16, plus strongly induced T cell (mainly CD4-positive) and humoral immune responses in all patients vaccinated.

For more information see: ClinicalTrials.gov

VicOryx 02 Combination Trial

VicOryx was additionally tested in a Phase I/IIa trial in combination with standard cisplatin-based chemotherapy to confirm the positive results of the previous trial. This additional trial was an open label study at a single center in patients with HPV-associated anogenital (cervical, vulvar, vaginal, penile, and anal) tumor diseases or HPV-associated head and neck cancer who are scheduled to receive a cisplatin-based chemotherapy.

Primary objectives were the feasibility of vaccination during the chemotherapy and a specific immune response against p16INK4a.

Secondary objectives included safety, progression-free survival and overall survival as well as a tumor response according to Response Evaluation Criteria In Solid Tumors (RECIST).

Results: The vaccine in combination with standard cisplatin-based chemotherapy showed excellent safety and tolerability.

For more information see: ClinicalTrials.gov