Safety, tolerability and immunogenicity of V934/V935 hTERT vaccination in cancer patients with selected solid tumors: a phase I study.

BACKGROUND: Human telomerase reverse transcriptase (hTERT) is an antigen that may represent a target for a novel anti-cancer strategy. A pilot, phase I study tested the safety and feasibility of a prime-boost immunization regimen based on V935, an adenoviral type 6 vector vaccine expressing a modified version of hTERT, administered alone or in combination with V934, a DNA plasmid that also expresses the same antigen and is delivered using the electroporation injection technique. METHODS: Treatments: Group #1 received two doses (low-dose: 0.5 × 109 vg, and high-dose: 0.5 × 1011 vg) of V935 followed by a 4-week observation period. Group #2 received three doses of V934-electroporation and two doses of V935 following a 4-week observation period. Doses were low-dose V934 (0.25 mg of plasmid) with low-dose V935 (0.5 × 109 vg); high-dose V934 (2.5 mg of plasmid) with high-dose V935 (0.5 × 1011 vg). Group #3 received five doses of V934-EP and two doses of V935: V934 was administered IM every 2 weeks for five doses. Following a 4-week observation period, V935 was administered IM every 2 weeks for two doses followed by a 4-week observation period. One (1) dose level was tested in treatment group #3: high-dose V934 (2.5 mg of plasmid), in combination with high-dose V935 (0.5 × 1011 vg). Immunogenicity was measured by ELISPOT assay and three pools of peptides encompassing the sequence of hTERT. RESULTS: In total, 37 patients affected by solid tumors (prostate cancer in 38%) were enrolled. The safety profile of different regimens was good and comparable across groups, with no severe adverse events, dose-limiting toxicities or treatment discontinuations. As expected, the most common adverse events were local reactions. A significant increase in ELISPOT responses against hTERT peptide pool 2 was observed (p < 0.01), while no evidence of boosting was observed for peptide pools 1 and 3. This was also evident for group #1 and #2 separately. In patients with prostate cancer, there was a significant increase in ELISPOT response against hTERT peptide pool 2 following immunization (p < 0.01), regardless of previous therapy, immunosuppressing agents, or adenoviral type 6 titers at screening. CONCLUSION: Our results suggest the safety and feasibility of V934/V935 hTERT vaccination in cancer patients with solid tumors Trial Registration Name of the registry: ClinicalTrial.gov Trial registration number: NCT00753415 Date of registration: 16 September 2008 Retrospectively registered URL of trial registry record: https://clinicaltrials.gov/ct2/results?cond=&term=NCT00753415&cntry=&state=&city=&dist=.