A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal cell carcinoma (RCC)

2581 Background: MUC1 is a glycoprotein often over-expressed and underglycosylated in renal cell carcinoma (RCC) making it an attractive antigenic target for tumor-specific immunotherapy. TG4010 is a cancer vaccine based on a modified vaccinia virus, strain MVA, expressing both MUC1 and Interleukin 2 (MVA-MUC1-IL2). The objective of this phase II, non-randomized study was to determine the efficacy of TG4010 alone and in combination with cytokines. Methods: Thirty seven patients (pts) with progressive metastatic RCC expressing MUC1 in at least 50% of the tumour cells were treated by subcutaneous injections of TG4010, 108 pfu/inj weekly, for 6 weeks then every three weeks until progression. At progression, TG4010 was continued in combination with Interferon α2a (INF) and Interleukin 2 (IL2). Results: Treatment efficacy and toxicities were previously presented at ASCO 2005 (abstr 4653). No objective responses have been observed, however, 7 pts (19%) remained stable for more than 6 months with TG4010 alone, 3 of them more than 22 months. After progression on TG4010 alone 22 pts received TG4010 in combination with cytokines. Six pts (27%) have been stabilized more than 6 months. The median TTP were 2.6 months (95% CI, 2.4–2.9 months) for TG4010 alone and 3.5 months (95% CI, 0.2–6.7 months) for the combined treatment. There were 24 deaths, with a median OS of 19 months (95% CI, 10–27.9) for the whole population. Seven pts were treated by sorafenib after immunotherapy failure. After censoring pts at the introduction of sorafenib, the median OS was 16 months (95% CI, 6–26), with 41% of pts alive at 2-years. The most frequent adverse effects related to TG4010 were minor to moderate injection site reactions, fatigue and flu-like symptoms. Twelve out of 24 pts evaluable for MUC1 ELISpot show evidence for MUC1-specific CD8+ T cell response while 14 out of 21 evaluable for MUC1 specific T cell proliferation were responsive. Conclusions: The cancer vaccine TG4010 alone and in combination with IL2 and INF induces some disease stabilizations in pts with progressive metastatic RCC and can improve survival in a population selected for MUC1 positivity, which is a factor of poor prognosis. [Table: see text]