Phase 1 Trial With the Cell-Based Immune Primer Ilixadencel, Alone, and Combined With Sorafenib, in Advanced Hepatocellular Carcinoma

Abstract

Several lines of evidence support immunotherapy in hepatocellular carcinoma (HCC). We have shown that intratumoral injections of the immune primer ilixadencel (pro-inflammatory allogeneic dendritic cells) are safe in renal-cell carcinoma. Here, we assessed ilixadencel as a single agent and combined with sorafenib in advanced HCC. Of 17 HCC patients enrolled, 12 patients received ilixadencel at the dose of 10 × 106 cells (six as monotherapy and six in combination with sorafenib), and five received ilixadencel at the dose of 20 × 106 cells as monotherapy. The primary objective was to evaluate tolerability. All patients had at least one adverse event, with 30% of such events considered as treatment-related, with one single treatment-related grade three event. The most common toxicity was grade 1 and 2 fever and chills. Eleven of 15 evaluable patients (73%) showed increased frequency of tumor-specific CD8+ T cells in peripheral blood. Overall one patient had a partial response (with ilixadencel as monotherapy), and five had stable disease as overall best response per mRECIST. The median time to progression was 5.5 months, and overall survival ranged from 1.6 to 21.4 months. Our study confirms the safety of ilixadencel as single agent or in combination with sorafenib and indicates tumor-specific immunological responses in advanced HCC. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01974661.

Keywords: allogeneic; cell therapy; dendritic cells; hepatocellular carcinoma; ilixadencel; immunotherapy; sorafenib.

Figures

Figure 1

T-cell activation in mixed leukocyte reaction with allogeneic PBMCs and ilixadencel. CD3+ T-cell proliferation after 5 days in a mixed leukocyte reaction with allogeneic PBMCs and in the presence of ilixadencel. The effect of ilixadencel on PBMCs from five different donors was assessed in combination with sunitinib (0.1 μg/mL), sorafenib (1 μg/mL) or anti-PD-1 antibody (20 μg/mL; and defined as anti-PD1 in bar), and compared to control (Ctrl), containing ilixadencel and allogeneic PBMCs. CD3 staining was used to allow identification of the responding proliferating T cells by flow cytometry. Results are shown as the percentage of CD3+ T proliferating cells and each bar represents mean ± standard deviation (n = 5). Statistical significant differences were analyzed using Student's t-test. **P < 0.01.