Immune Responses And Association With Clinical Outcome Of Advanced Colorectal Cancer Patients Treated With The Multi-Peptide Vaccine Ima910.

2522 Background: IMA910 is a novel multi-peptide cancer vaccine consisting of 10 HLA class I and 3class II tumor-associated peptides (TUMAPs), which were selected based on natural presentation on colorectal tumors by the XPRESIDENT antigen discovery platform. Methods: 92 HLA-A*02+ advanced colorectal cancer (aCRC) patients (pts) with stable or responding disease after 12 weeks of first-line oxaliplatin-based therapy were enrolled in this phase I/II trial. After pre-treatment with cyclophosphamide (300 mg/m2), patients were immunized intradermally with IMA910 plus the immune modulator GM-CSF without (cohort 1; n=66) or with (cohort 2; n=26) topically applied imiquimod, another immune modulator acting via toll-like receptor 7 on antigen presenting cells. T-cell responses to individual IMA910 peptides were analyzed by HLA multimer and intracellular cytokine staining (ICS) assays. Results: IMA910 elicited immune responses towards multiple class I (43%) and class II TUMAPs (65%). 34% of pts responded to multiple class I and class II TUMAPs. Pts that received imiquimod were more often multi-peptide class I responders in the ICS assay (p=0.016) and showed an approx. 2x higher frequency of T-cell response (p=0.12). Responses to multiple class I and class II TUMAPs were associated with higher disease control rate at all time points (all p<0.02), increased time to progression (p=0.006), progression-free survival (p=0.009) and OS (p=0.088, HR=0.53). Baseline characteristics of multi vs. non-multi responders were overall well comparable. In a prospectively defined, blinded matched-pair analysis with patients in arm C of the COIN trial, multi-peptide responder patients showed a prolonged survival vs. corresponding COIN patients (p=0.04), while the non-multi responder patients had comparable survival. Conclusions: IMA910 is immunogenic. Imiquimod increases the quality of immune responses. Responses to multiple TUMAPs are associated with better clinical outcome. Several observations indicate that this association is not a reflection of better prognosis of the immunologically responding subset of patients. These results suggest further development of IMA910.