Results of a randomized phase II study investigating multipeptide vaccination with IMA901 in advanced renal cell carcinoma (RCC).

Abstract

4529 Background: IMA901 is a therapeutic cancer vaccine based on the selection of naturally presented tumor-associated peptides (9 HLA-class I- and 1 HLA class II-binding peptides). A previous phase I study showed a significant correlation of disease control rate (DCR) at 3 mo with T-cell responses to multiple IMA901 peptides but no correlation to a vaccinated control peptide. Methods: HLA-A*02+ patients with clear-cell RCC and documented progression during or after first-line cytokine- or TKI-based therapy were randomized 1:1 to receive up to 17 intradermal vaccinations of IMA901 over 9 mo together with 75 μ g GM-CSF ± a single infusion of low-dose cyclophosphamide (Cy; 300 mg/m2) before the first vaccination. Stratification included MSKCC risk group (low or intermediate risk) and first-line therapy (cytokines or TKI). Primary endpoint was DCR at 6 mo. Secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and peptide-specific T-cell responses. Results: 68 patients were treated. DCR at 6 mo was 31% in the post-cytokine group (n=40) and 12% in the post-TKI group (n=28). Median OS has not yet been reached with OS rates in post-cytokine patients being particularly encouraging (Table). Furthermore, a strong trend toward better outcome (DCR at 6 mo and OS) was seen in patients with multiple T-cell responses against IMA901. Patients who received pretreatment with Cy showed a decrease of regulatory T-cells (Treg) levels and multipeptide responders in this group had significantly better OS than others (p=0.019; no death recorded in this group thus far). The safety profile was confirmed to be favorable with most AE being local injection-site reactions. Conclusions: This phase II study confirmed that IMA901 is safe, well tolerated, and immunogenic. Overall survival compares favorably with published results from currently approved drugs. OS rate at 6 mo OS rate at 12 mo OS rate at 18 mo All patients (n=68) 77% 67% 54% Patients 2nd-line post cytokines (n=40) 87% 79% 68% Patients 2nd-line post cytokines(Cy pretreatment; n=20) 90% 83% 83% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immatics Immatics Immatics