A phase I study to evaluate safety, immunogenicity and anti-tumor activity of the multi-peptide vaccine IMA901 in renal cell carcinoma patients (RCC)
5098 Background: IMA901 is a therapeutic cancer vaccine based on multiple synthetic tumor-associated peptides confirmed to be naturally presented by analysis of primary RCC tissues. IMA901 consists of 9 HLA-class I-binding and 1 HLA class II-binding peptides with the capacity to activate cytotoxic T cells (CD8+ T cells) and T helper cells (CD4+ T cells). Methods: 30 patients with stage III/IV RCC were enrolled in a single arm, multi-centre study. The endpoints were safety, T-cell responses, pharmacokinetics of the intradermal application of GM-CSF and anti-tumor activity according to RECIST. Patients had to be HLA-A*02 positive and received 8 intradermal vaccinations on days 1, 2, 3, 8, 15, 22, 36 and 64 each consisting of 4.5 mg IMA901 and 75 μg GM-CSF. Results: The most prevalent adverse events (AEs) were fatigue, cough and headache. Aseptical lymphadenitis and injection site reactions such as erythema, edema and pruritus were the most frequent possibly drug-related AEs. All possibly drug-related adverse events were mild to moderate. No patient experienced any possibly drug-related serious adverse events or deaths during the study. Pharmacokinetic data provided no evidence for accumulation of GM-CSF upon repeated i.d. administration. 74% of patients showed a vaccine-induced specific T-cell response and 30% of patients responded to multiple peptides contained in IMA901. The overall tumor assessment in patients with measurable disease revealed that 8 patients (35%) demonstrated a clinical benefit (1 PR + 7 SD). Most encouraging, patients who elicited multiple T-cell responses showed a statistically significant higher clinical benefit rate. Conclusions: IMA901 is safe, very well tolerated and immunogenic. Clinically observed tumor growth control in RCC patients may imply anti-tumor activity strongly supported by two patients with tumor regression (1 PR and 1 patient with 27% shrinkage in target lesions). The mode of action is strongly supported by the finding that multiple T-cell responders were significantly more likely to have a clinical benefit. These data clearly support the further development of IMA901. No significant financial relationships to disclose.