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Author Notes:

Correspondence: Asim.Amin@carolinashealthcare.org; robert.figlin@cshs.org.

All authors participated in manuscript writing, review and revision.

In addition, AA participated in study conception and design, method development, data acquisition, analysis and interpretation and study supervision.

AZD, TFL, RSL, JMH, JJK, SKP, WHM, and LIK participated in study conception and design, method development, data acquisition, and study supervision.

VAM participated in study conception and design, method development, and study supervision.

IYT participated in data analysis and interpretation and technical and materials support.

MADeB participated in data acquisition, analysis and interpretation and technical and materials support.

WLW participated in data analysis and interpretation and study administration.

DCP participated in data analysis and interpretation, study administration and study supervision.

CAN participated in study conception and design, method development, data analysis and interpretation and study administration.

RAF participated in data analysis and interpretation, and study supervision.

Patrice C. Ferriola provided editorial assistance in the preparation for the manuscript and was supported by Argos Therapeutics, Inc.

For authors' competing interests, please see the full article.

Subjects:

Keywords:

  • AGS-003
  • Dendritic cell
  • Immunotherapy
  • RCC
  • Sunitinib

Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results.

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Journal Title:

Journal for ImmunoTherapy of Cancer

Volume:

Volume 3, Number 1

Publisher:

, Pages 14-14

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: AGS-003 is an autologous immunotherapy prepared from fully matured and optimized monocyte-derived dendritic cells, which are co-electroporated with amplified tumor RNA plus synthetic CD40L RNA. AGS-003 was evaluated in combination with sunitinib in an open label phase 2 study in intermediate and poor risk, treatment naïve patients with metastatic clear cell renal cell carcinoma (mRCC). Methods: Twenty-one intermediate and poor risk patients were treated continuously with sunitinib (4 weeks on, 2 weeks off per 6 week cycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3 weeks for 5 doses, then every 12 weeks until progression or end of study. The primary endpoint was to determine the complete response rate. Secondary endpoints included clinical benefit, safety, progression free survival (PFS) and overall survival (OS). Immunologic response was also monitored. Results: Thirteen patients (62%) experienced clinical benefit (9 partial responses, 4 with stable disease); however there were no complete responses in this group of intermediate and poor risk mRCC patients and enrollment was terminated early. Median PFS from registration was 11.2 months (95% CI 6.0, 19.4) and the median OS from registration was 30.2 months (95% CI 9.4, 57.1) for all patients. Seven (33%) patients survived for at least 4.5 years, while five (24%) survived for more than 5 years, including 2 patients who remain progression-free with durable responses for more than 5 years at the time of this report. AGS-003 was well tolerated with only mild injection-site reactions. The most common adverse events were related to expected toxicity from sunitinib therapy. In patients who had sequential samples available for immune monitoring, the magnitude of the increase in the absolute number of CD8+ CD28+ CD45RA− effector/memory T cells (CTLs) after 5 doses of AGS-003 relative to baseline, correlated with overall survival. Conclusions: AGS-003 in combination with sunitinib was well tolerated and yielded supportive immunologic responses coupled with extension of median and long-term survival in an unselected, intermediate and poor risk prognosis mRCC population.

Copyright information:

© 2015 Amin et al.; licensee BioMed Central. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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