Introduction

IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed?to be naturally presented in human cancer tissue. We reported the effectiveness of the vaccine in phase 1 and 2 trial in Europe and US (IMA901-202 study) (Walter S, et al. Nat Med. 2012; 18: 1254-61). A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing in Europe and US. The objective of our study was to assess the safety and tolerability of IMA901 vaccination for the Japanese metastatic RCC patients.

Methods

In this phase 1 and 2 study in Japan (IMA901-IJ1), we treated a total of 10 Japanese patients with advanced RCC with human leukocyte antigen A (HLA-A)*02 + subjects in 2011-2012. Each of the vaccinations consisted of an i.d. injection of GM-CSF (75 ?g) followed within 15-30 minutes by an i.d. injection of IMA901 (413 ?g of each peptide). The vaccine therapy was a monotherapy, i.e., no other anti-tumor therapies were concomitantly administered during the study course. No treatment with either anti-cancer agents or immunosuppressants was allowed within 4 weeks before entering the trial. Patients were to receive 7 vaccinations in the first 5 weeks of treatment (induction period) followed by 10 further vaccinations at 3 weeks intervals for up to 30 weeks (maintenance period). The primary endpoint was safety and tolerability. The secondary endpoints were PFS, OS, immunogenicity.

Results

No treatment-related serious adverse events (SAEs) or deaths were observed during the study period. At follow-up at 4 months, all cases were assessed for treatment response. 10% of patients had partial response (PR), 50% with stable disease (SD), 40% of patients had progressive disease (PD). Median PFS was 5.5 months and median OS was 18.0 months. Among all patients analyzed for T-cell response, five showed vaccine-induced (VI) T-cell responses? against at least one HLA class I-restricted TUMAP and two patients with responses to multiple TUMAPs (Figure 1). The T-cell response rate in this study was similar to our previous study in Europe and US. Interestingly, two of the immune responders were of HLA-A*0206 phenotype, a HLA suballele rarely occurring in Europe and US but common in Japan.

Conclusions

This study showed safety and tolerability of IMA901 vaccination and immune responses in Japanese RCC patients. _x000D_

Funding

none