Clinical outcome of patients with various advanced cancer types vaccinated with an optimized cryptic human telomerase reverse transcriptase (TERT) peptide: results of an expanded phase II study

Background: TERT (telomerase reverse transcriptase) plays a critical role in tumor cell growth and survival. In an expanded phase II study, we evaluated the immunological and clinical responses to the TERT-targeting Vx-001 vaccine in patients with advanced solid tumors. Methods: HLA-A*0201-positive patients received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide, every 3 weeks. Peptide-specific immune responses were evaluated by enzyme-linked immunosorbent spot at baseline, and after the second and the sixth vaccinations. Results: Fifty-five patients were enrolled and 34 (62%) completed the six vaccinations. A TERT-specific T-cell immune response was observed in 55% and 70% of patients after the second and the sixth vaccinations, respectively. The disease control rate (DCR) was 36% [95% confidence interval (CI) 24% to 49%], including one complete and one partial response. Immunologically responding patients had a better clinical outcome than nonresponders [DCR: 44% versus 14% (P = 0.047); progression-free survival (PFS): 5.2 versus 2.2 months (P = 0.0001) and overall survival: 20 versus 10 months (P = 0.041)]. Multivariate analysis revealed that the immunological response was an independent variable associated with increased PFS (hazard ratio = 3.35; 95% CI 1.7-6.7). Conclusion: Vx-001 vaccine was well tolerated and induced a TERT-specific immunological response, which was significantly correlated with improved clinical outcome.