Abstract CT021: INVAC-1, an optimized telomerase DNA vaccine in patients with advanced solid tumors: Final results of first-in-human phase I study

Background INVAC-1 is an optimized DNA plasmid encoding an inactive form of human Telomerase Reverse Transcriptase (hTERT), a universal tumor antigen expressed in most of human tumors with little or no expression in normal somatic cells. Primary pharmacodynamics, safety and toxicology studies showed that INVAC-1 was enzymatically inactive, immunogenically safe and well tolerated. In murine models, we demonstrated that INVAC-1 was able to induce hTERT specific cellular immune responses with CD4+ Th1 effector and memory CD8+ T-cells as well as slow tumor growth and increase survival rate by 50% in tumor-bearing mice. Methods We conducted a First-In-Human (FIH) study, 2-centre, Phase I, open label, 3+3 escalation design and multiple dose study examining the safety and tolerability of INVAC-1 administered at three dose levels (100, 400 and 800 µg) in 26 patients with relapsed or solid refractory tumors. INVAC-1 was administered either by intradermal (ID) injection followed by electroporation (EP) (n=20) or by Tropis® Needle Free Injection System (n=6). Results INVAC-1 vaccination was safe and well tolerated when administered ID (either with EP or by Tropis®) at the three tested doses. Only one treatment-related grade 3 SAE was reported. 58% of patients experienced disease stabilization up to 9.9 months. One-year survival was reached for 65% of patients. INVAC-1 elicited both hTERT specific Th1-dominant CD4 and cytotoxic CD8 T cell responses with no vaccine-induced peripheral immunosuppression. Anti-hTERT immune responses were enhanced by adding anti-PD-1 immune checkpoint inhibitor ex vivo. In addition, INVAC-1 vaccination was able to promote epitope spreading. Finally, correlation analysis between clinical and immunological data showed that patients with OS >1 year presented a significantly higher hTERT immune response after INVAC-1 vaccination compared to patients with OS Citation Format: Julie Garibal, Jacques Medioni, Luis Teixeira, Olivier Adotevi, Marie-Agnes Dragon-Durey, Caroline Laheurte, Claire Germain, Marie Escande, Maria Wehbe, Valerie Doppler, Thierry Huet, Pierre Langlade Demoyen. INVAC-1, an optimized telomerase DNA vaccine in patients with advanced solid tumors: Final results of first-in-human phase I study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT021.