In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 3007-3007
Abstract:
3007 Background: Hyperacute rejection of tissues expressing the carbohydrate α(1,3)Gal xenoantigen is a potent innate immune defense mechanism that was leveraged to treat resected pancreatic cancer patients by immunization with genetically modified allogeneic tumor cells expressing αGal moieties (algenpantucel-L). We propose that adding algenpantucel-L to SOC adjuvant therapy may improve survival and induce immunological biomarkers that positively correlate with improved median overall survival (OS). Methods: Open-label, multicenter phase II study evaluating algenpantucel-L+SOC (RTOG-9704: gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Endpoints: 1°) disease-free survival (DFS) at 1 year; 2°) OS, toxicity and immunologic analysis. Biomarkers were evaluated including total IgG, complement, CA19-9 levels, anti-αGal Ab, anti-CEA Ab, and anti-membrane-bound recombinant mesothelin (MSLN) Ab. Results: Patients received gemcitabine with 5-FU modulated radiation therapy plus algenpantucel-L. The primary endpoint, 12-month DFS, was 62% and 12-month OS was 86%. All evaluable patients have been in follow-up for ≥ 3 years. We now report OS rates at 3 years of 39% and DFS of 26% at 3 years. Evaluable patients (n=64) were tested for the induction of anti-MSLN Ab where ≥ 25% increase in the anti-MSLN Ab compared to baseline was considered significant (p 〈 0.001). Twenty of 64 patients (31%) had increased anti-MSLN Ab. Patients responding with anti-MSLN Ab had a median OS of 42 months compared to 20 months for patients without sero-conversion. The positive correlation between increased anti-MSLN Ab and improved median OS was statistically significant (p=0.027). Conclusions: The addition of algenpantucel-L to SOC for resected pancreatic cancer may improve survival. In 20/64 patients, algenpantucel-L-induced anti-MSLN Ab responses that correlates with improved survival (median OS 42 vs 20 months). Immunological monitoring of algenpantucel-L immunotherapy with this biomarker is feasible and might predict patient response to therapy. A multi-institutional, phase III study is currently underway (ClinicalTrials.gov NCT01072981). Clinical trial information: NCT00569387.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.3007
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
