A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

Tim F Greten, Alejandro Forner, Firouzeh Korangy, Gisele N'Kontchou, Nathalie Barget, Carmen Ayuso, Lars A Ormandy, Michael P Manns, Michel Beaugrand, Jordi Bruix, Tim F Greten, Alejandro Forner, Firouzeh Korangy, Gisele N'Kontchou, Nathalie Barget, Carmen Ayuso, Lars A Ormandy, Michael P Manns, Michel Beaugrand, Jordi Bruix

Abstract

Background: The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC.

Methods: 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses.

Results: None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination.

Conclusions: Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC.

Trial registration: NCT00444782.

Figures

Figure 1
Figure 1
Kaplan-Meier Analysis of Time to Progression (TTP) and Time to Symptomatic Progression (TTSP). The median TTP was 57 days (1.9 months) and the TTSP was 358 days (11.7 months).
Figure 2
Figure 2
Kaplan-Meier Analysis of Overall Survival and Progression Free Survival. Among 40 patients, the median overall survival was 358 days (11.7 months) and the progression free survival was 57 days (1.9 months).
Figure 3
Figure 3
Analysis of CD4+CD25+Foxp3+ regulatory T cells in HCC patients prior to cyclophosphamide treatment and after 5 days.
Figure 4
Figure 4
Analysis of GV1001 specific T cell responses by ELISA (A) and thymidine incorporation (B) in HCC patients before and after peptide vaccination. Among 11 patients analyzed no definite antigen-specific T cell responses were noticed.

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Source: PubMed

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