Abstract 2232: Immune-inflammatory markers predict the outcome of metastatic colorectal cancer patients treated with the thymidylate synthase poly-epitope peptide (TSPP) vaccine: results from a multi-arm TSPP/VAC phase Ib program
Authors: Correale Pierpaolo , Botta Cirino , Martino Elodia Claudia , Nardone Valerio , Ulivieri Cristina , Gandolfo Claudia , Baldari Tatiana Cosima , Lazzi Stefano , Ginori Alessandro , Fioravanti Antonella , Guidelli Giacomo Maria , Pirtoli Luigi , Giordano Antonio , Tassone Pierfrancesco , Tagliaferri Pierosandro , Cusi Maria Grazia 
Published: July 2016

Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication. TSPP is a poly-epitope-peptide vaccine to TS, which elicits a multi-epitopic CTL response with antitumor activity in preclinical models. TSPP has been tested in 50 advanced cancer patients enrolled in a multi-arm dose-finding TSPP/VAC1 phase Ib trial program (Eudract:# 2009-016897-33)(Table1) between May 2011 and January 2013. The trial results revealed that TSPP is safe and immune-biologically active, and provided preliminary evidence of a antitumor activity in pretreated mCRC patients (Cusi MG et al 2015 and Correale P et al 2015). This population of 41 patients presented a progression-free-survival and an overall-survival (OS) of 6.9 and 11.3 months, respectively, with a one-year survival rate of 32% (13 patients). We focused on mCRC patients as they represented the most relevant and homogeneous population in the trial. We performed Kaplan-Meier curves, log-rank tests and regression curves to correlate immunobiological findings and patients’ outcome. We found that their OS correlated with lower (under the median) ECOG scores (p:0.039), CEA levels (p:0.021), and serum levels of inflammatory markers (NLR, CRP, ESR, and LDH/LDHNR and ENA; p inferior 0.04) at baseline. Patients’ OS also correlated with greater (over the median) baseline levels of IL4 (p:0.028) and 17 (P:0.049), and with a post-treatment increase in anti-neutrophil-cytoplasm-antibodies/anti-proteinase-3 (Fold change to baseline values grater than 1; p:0.039). Activating K-ras mutations did not correlate with survival, however, inflammatory markers, cytokines, and autoantibodies lost their correlation with the survival in patients bearing these mutations. These results suggest that TSPP-antitumor activity in mCRC patients is affected by their baseline inflammatory/immunological status at baseline. TSPPVAC1 Phase Ib program; patients’ distributionARM A1. ADJ + TSPP 100 μg (n = 3)2. ADJ + TSPP 200 μg (n = 3)3. ADJ + TSPP 300 μg (n = 6)ARM B1. ADJ + TSPP 100 μg + IG-1 (n = 3)2. ADJ + TSPP 200 μg + IG-1 (n = 3)3. ADJ + TSPP 300 μg + IG-1 (n = 3)ARM C (DL1-3)1. GOLFIG + ADJ+TSPP 100 μg + IG-1 (n = 3)2. GOLFIG + ADJ+TSPP 200 μg + IG-1 (n = 3)3. GOLFIG + ADJ+TSPP 300 μg + IG-1 (n = 11)ARM C(DL0) 1. GOLFIG (12 courses) -&gt; ADJ + TSPP 300 μg + IG-1 (n = 10)Figure legend: ADJ = montanide; n = number of patients; IG1 = sc. GM-CSF and sc. Aldesleukine; GOLFIG = gemcitabine + FOLFOX4 polychemotherapy + IG1 regimen

Citation Format: Pierpaolo Correale, Cirino Botta, Elodia Claudia Martino, Valerio Nardone, Cristina Ulivieri, Claudia Gandolfo, Tatiana Cosima Baldari, Stefano Lazzi, Alessandro Ginori, Antonella Fioravanti, Giacomo Maria Guidelli, Luigi Pirtoli, Antonio Giordano, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Grazia Cusi. Immune-inflammatory markers predict the outcome of metastatic colorectal cancer patients treated with the thymidylate synthase poly-epitope peptide (TSPP) vaccine: results from a multi-arm TSPP/VAC phase Ib program. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2232.