Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer
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In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases. Bone metastases were present in 17 (77%) patients and 16 (73%) patients had affected lymph nodes. Three dose levels of UV1 were given as intradermal injections combined with GM-CSF (Leukine®). Twenty-one patients in the intention-to-treat population (95%) received conformal radiotherapy. Adverse events reported were predominantly grade 1, most frequently injection site pruritus (86.4%). Serious adverse events considered possibly related to UV1 and/or GM-CSF included anaphylactic reaction in two patients and thrombocytopenia in one patient. Immune responses against UV1 peptides were confirmed in 18/21 evaluable patients (85.7%), PSA declined to <0.5 ng/mL in 14 (64%) patients and in ten patients (45%) no evidence of persisting tumour was seen on MRI in the prostatic gland. At the end of the nine-month reporting period for the study, 17 patients had clinically stable disease. Treatment with UV1 and GM-CSF gave few adverse events and induced specific immune responses in a large proportion of patients unselected for HLA type. The intermediate dose of 0.3 mg UV1 resulted in the highest proportion of, and most rapid UV1-specific immune responses with an acceptable safety profile. These results warrant further clinical studies in mPC.
KeywordsProstate cancer hTERT Cancer vaccine Immune response
Androgen deprivation therapy
Good clinical practice
Human telomerase reverse transcriptase
Prostate cancer clinical trials working group
We thank all the patients for their participation in the study. Furthermore, we also appreciate the excellent administrative assistance of Signe Fretland and Dovile Kuliesiute and thank Grete Berntsen for excellent technical assistance with immunomonitoring. We thank Ingunn Westgaard for critical reading of the manuscript.
This study was supported by The Norwegian Research Council (FORNY program), Innovation Norway AS, Ultimovacs AS.
Compliance with ethical standards
Conflict of interest
Gustav Gaudernack is an employee and a shareholder in Ultimovacs AS. Gustav Gaudernack and Else Marit Inderberg are inventors on the UV1 vaccine patent. All other authors declare that no conflict of interest exists.
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