Abstract

<jats:p> 555 </jats:p><jats:p> Background: Treatment interruption after 12 weeks of oxaliplatin-based therapy followed by re-introduction upon signs of progression results in better overall tolerability and quality of life compared to continuous therapy while survival rates are only modestly impaired. Specific immunotherapy may provide a safe and tolerable intervention to prolong time to re-introduction and eventually overall survival. IMA910 is a novel peptide-based cancer vaccine consisting of 13 tumor-associated peptides (TUMAPs), which are naturally presented on MHC molecules of colorectal tumors. </jats:p><jats:p> Methods: HLA-A*02<jats:sup>+</jats:sup> advanced CRC patients being at least clinically stable after 12 weeks of first-line oxaliplatin-based therapy were enrolled. After immunomodulation with a single low dose of cyclophosphamide (300 mg/m2), patients were immunized intradermally (up to 16 vaccinations) with IMA910 in combination with GM-CSF (cohort 1; n=66) or IMA910 with GM-CSF plus topically applied imiquimod (cohort 2; n=26). T-cell responses to individual IMA910 peptides were analyzed by HLA-multimer and intra-cellular cytokine assay. Analysis of disease control rates (DCR) and progression-free survival (PFS) was based on RECIST-centrally reviewed CT/ MRI scans. </jats:p><jats:p> Results: IMA910 was overall well tolerated with most AEs being mild and transient local site reactions. Three patients presented with systemic hypersensitivity reactions, all of which were observed after ≥10 vaccinations and were confirmed to have an in vitro reaction against GM-CSF in all cases. IMA910 induced immune responses in 71% and 72% of patients in the two cohorts, respectively. Interestingly, patients developing CD8 T-cell responses against multiple TUMAPs had a better clinical outcome compared to others, in terms of DCR (18% vs. 2% at 6 months; p=0.012) and PFS (HR: 0.652; p=0.039). OS data will be shown at the meeting. </jats:p><jats:p> Conclusions: Vaccination with IMA910 is safe, well tolerated, and immunogenic. Significantly better clinical outcome of multi-TUMAP responders in comparison to patients with one/no TUMAP response indicates clinical activity of IMA910 in 1<jats:sup>st</jats:sup> line advanced CRC patients. </jats:p>