Clinical and immune characteristics of rapid dropout and long-term survival in a phase II safety and efficacy study of combination CRS-207/GVAX immunotherapy in pancreatic cancer.

Abstract

459 Background: Baseline patient characteristics may impact duration on study and survivorship of patients in immunotherapy trials. In this study, GVAX pancreas (GM-CSF–secreting allogeneic pancreatic tumor cells) was administered with low-dose cyclophosphamide (Cy), with or without subsequent CRS-207 (live-attenuated Listeria monocytogenes–expressing mesothelin) infusion. Baseline clinical and immunological data were examined for two patient subsets based on duration on study. Methods: Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to 2 doses of Cy/GVAX followed by 4 doses of CRS-207 or 6 doses of Cy/GVAX every 3 weeks. Stable patients were offered additional courses. Patients were evaluated for post-randomization duration on study of < 60 days (rapid dropouts, RD) and > 18 months (long-term survivors, LTS). Baseline characteristics of these subsets were examined. Results: A total of 93 patients were randomized. Fifteen patients were RD; 13 were LTS. More RDs versus LTS had liver metastasis and lymph node involvement. On average, fewer RD patients had radiotherapy prior to randomization and fewer had prior surgical intervention. RD averaged 1.73 prior metastatic cancer treatment regimens versus 1.31 in LTS. RD also had higher average baseline CA 19-9 levels. Immune analysis showed higher circulating terminal effector CD8+ T cells and lower serum IL-6 in LTS compared to RD. Serum IL-6 concentration remained lower in LTS at four weeks following initiation of treatment. For patients who received CRS-207, CD8+ T cells specific to listeriolysin O (LLO) and mesothelin were higher in LTS than RD, as determined by ELISPOT. Conclusions: Baseline clinical and immunological characteristics may impact patient duration on immunotherapy trials. Immune monitoring and biomarker analysis in this study is ongoing to identify circulating cellular, tumor biomarkers and genomic (miRNA and mRNA) signatures that may correlate with survival. These findings warrant continued exploration of patient characteristics to identify best candidates for immunotherapy trials. Clinical trial information: NCT01417000.