In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 2561-2561
Abstract:
2561 Background: CEA is expressed in 〉 90% of PC and may be an appropriate immunotherapy target. CEA is poorly immunogenic due to immune tolerance; CAP1-6D, an altered peptide ligand can help bypass tolerance. We conducted a pilot randomized phase I trial in PC pts to determine the appropriate CEA-vac peptide dose required to induce an optimal cytotoxic T lymphocyte (CTL) response. Methods: Eligible pts, PS 0-1, expressed HLA-A2 and had CEA-expressing, histologically-confirmed, previously-treated PC. Randomization: 10 μg (arm A), 100 μg (arm B) or 1000 μg (arm C). CEA-vac was given Q 2 weeks until disease progression (amended 4/09 to a 24 dose maximum). Results: From 2/06-9/09 66 pts were screened for HLA-A2; 19 pts randomized to Arms A/B/C 5/8/6 are evaluable for toxicity; 14 pts (5/5/4) who received at least 3 doses of CEA-vac are evaluable for the primary immunologic endpoint. Median age: 60 (range 27-86), female: 68%, PS 0: 58%. Disease stage: metastatic (M) 74%, locally advanced (LA) 5%, resected (R) 21%. Cycles: median 4 (range 1-81). Mean CTL response by ELISPOT (spots per 10 4 CD8 + cells, Arm A/B/C): 37/126/248. (A vs. C, p=0.037). CTL responses developed in 20%/60%/100% of pts in Arms A/B/C. 1 LA pt in Arm C had a complete radiologic response, a strong CTL response, and remains alive at 71 mo. 1 M pt in Arm B had SD for 11 mo, a strong CTL response, and is alive at 39 mo. Toxicity: no grade 3/4 toxicities, 58% grade 1/2 skin toxicity. Conclusions: CTL response was dose-dependent in this randomized phase I trial; the 1 mg peptide dose elicited the most robust CTL response. Clinical activity was demonstrated at the higher doses. Further evaluation of 1 mg CEA-vac with stronger adjuvants, combined with agents to overcome immune inhibitory pathways, may be warranted in PC pts. Supported by UCCCSG P30CA14599.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.2561
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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