A First-in-Human Phase I Study of INVAC-1, an Optimized Human Telomerase DNA Vaccine in Patients with Advanced Solid Tumors

Purpose: Human telomerase reverse transcriptase(hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response and immunogenicityof INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors. Experimental Design: INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis®, a needle-free injection system. Safetyand tolerability were monitored by clinical and laboratory assessments. Progression-Free Survival and Overall Survival were reported using Kaplan-Meier survival analysis. Immunogenicitywas studied by ELISpot, Luminex® and Flow Cytometry. Results: 26 patients were treated with INVAC-1 administered at three dose levels (100, 400 and 800 µg). Vaccination was well tolerated and no Dose Limiting Toxicity was reported. One treatment-related grade 3 SAE was reported. 58% of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months and one-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti‑hTERT CD4 T cell response as well as cytotoxic CD8 T cell response. No evidence of peripheral vaccine-induced immune suppression was observed. Conclusions: INVAC-1 vaccination was safe, well tolerated and immunogenicwhen administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond.