Overall survival (OS) of advanced colorectal cancer (aCRC) patients (pts) treated with the multipeptide vaccine IMA910: Results of a matched-pair analysis with arm C pts from COIN.

Abstract

3530 Background: IMA910 is a novel cancer vaccine consisting of 10 class I and 3 class II tumor-associated peptides (TUMAPs), naturally presented on HLA molecules of CRC. Vaccine-induced immune responses are associated with prolonged OS of renal cell carcinoma pts treated with IMA901, a multi-peptide vaccine identified by the same antigen discovery platform. Methods: 92 HLA-A*02+ aCRC pts with stable or responding disease after 12 weeks of first-line oxaliplatin-based therapy were enrolled in this phase I/II trial. After immunomodulation with cyclophosphamide (300 mg/m2) to reduce regulatory T cells, pts were immunized intradermally (up to 16 vaccinations) with IMA910 in combination with GM-CSF without (cohort 1; n=66) or with (cohort 2; n=26) topically applied imiquimod. Safety and PFS data was recently presented [Mayer et al., ASCO-GI 2012]. OS of IMA910 pts was compared to matched pts from arm C (intermittent chemotherapy) of the COIN trial [Adams et al., Lancet Oncology 2011]. Matching was performed in a prospectively defined, fully blinded fashion based on a propensity score involving all available prognostic factors. T-cell responses to individual IMA910 peptides were analyzed by HLA multimer and intracellular cytokine assays. Results: At a median follow up of 1.7 yrs, OS of IMA910 vaccinated pts was significantly longer in comparison to 1:1 matched HLA-A*02+ COIN pts (HR 0.675, 95% CI 0.458-0.995, p=0.047; 1 yr OS: 69% vs 55%; 2 yr OS: 40% vs 24%). Multi-TUMAP responders (≥2 CD8+ and ≥2 CD4+ vaccine-induced T cells) had a significantly longer OS (HR 0.45, p=0.04) compared to matched COIN pts while non-multi-TUMAP responders showed similar OS compared to matched COIN pts (HR 0.76, p=0.22). Conclusions: OS of IMA910 pts was significantly longer in comparison to matched COIN pts with separation of survival curves at ~9 months and increasing OS difference over time. Multi-TUMAP immune responders had a significantly longer OS compared to non-multi-TUMAP responders and compared to matched COIN pts. These clinical and immune response data strongly suggest clinical activity of IMA910 in 1st line CRC pts and warrant further development.