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

Asim Amin, Arkadiusz Z. Dudek, Theodore Logan, Raymond S. Lance, Jeffrey M. Holzbeierlein, Jennifer J. Knox, Viraj A. Master, Sumanta K. Pal, Wilson H. Miller, Lawrence I. Karsh, Irina Y. Tcherepanova, Mark A. DeBenedette, W. Lee Williams, Douglas C. Plessinger, Charles A. Nicolette, Robert A. Figlin

Research output: Contribution to journalArticle

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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 (4weeks on, 2weeks off per 6weekcycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3weeks for 5 doses, then every 12weeks 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 11.2months (95% CI 6.0, 19.4) and the median OS from registration was 30.2months (95% CI 9.4, 57.1) for all patients. Seven (33%) patients survived for at least 4.5years, while five (24%) survived for more than 5years, including 2 patients who remain progression-free with durable responses for more than 5years 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. Clinical Trial Registry: NCT00678119

Original languageEnglish (US)
Article number14
JournalJournal for ImmunoTherapy of Cancer
Volume3
Issue number1
DOIs
StatePublished - Apr 21 2015

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Renal Cell Carcinoma
Immunotherapy
Dendritic Cells
Survival
Disease-Free Survival
RNA
sunitinib
Immunologic Monitoring
CD40 Ligand
Registries
Monocytes
Clinical Trials
T-Lymphocytes
Safety
Injections
Therapeutics
Population

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Immunology and Allergy
  • Cancer Research
  • Molecular Medicine
  • Pharmacology
  • Immunology

Cite this

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. / Amin, Asim; Dudek, Arkadiusz Z.; Logan, Theodore; Lance, Raymond S.; Holzbeierlein, Jeffrey M.; Knox, Jennifer J.; Master, Viraj A.; Pal, Sumanta K.; Miller, Wilson H.; Karsh, Lawrence I.; Tcherepanova, Irina Y.; DeBenedette, Mark A.; Williams, W. Lee; Plessinger, Douglas C.; Nicolette, Charles A.; Figlin, Robert A.

In: Journal for ImmunoTherapy of Cancer, Vol. 3, No. 1, 14, 21.04.2015.

Research output: Contribution to journalArticle

Amin, A, Dudek, AZ, Logan, T, Lance, RS, Holzbeierlein, JM, Knox, JJ, Master, VA, Pal, SK, Miller, WH, Karsh, LI, Tcherepanova, IY, DeBenedette, MA, Williams, WL, Plessinger, DC, Nicolette, CA & Figlin, RA 2015, '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', Journal for ImmunoTherapy of Cancer, vol. 3, no. 1, 14. https://doi.org/10.1186/s40425-015-0055-3
Amin, Asim ; Dudek, Arkadiusz Z. ; Logan, Theodore ; Lance, Raymond S. ; Holzbeierlein, Jeffrey M. ; Knox, Jennifer J. ; Master, Viraj A. ; Pal, Sumanta K. ; Miller, Wilson H. ; Karsh, Lawrence I. ; Tcherepanova, Irina Y. ; DeBenedette, Mark A. ; Williams, W. Lee ; Plessinger, Douglas C. ; Nicolette, Charles A. ; Figlin, Robert A. / 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. In: Journal for ImmunoTherapy of Cancer. 2015 ; Vol. 3, No. 1.
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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 na{\"i}ve patients with metastatic clear cell renal cell carcinoma (mRCC). Methods: Twenty-one intermediate and poor risk patients were treated continuously with sunitinib (4weeks on, 2weeks off per 6weekcycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3weeks for 5 doses, then every 12weeks 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 11.2months (95{\%} CI 6.0, 19.4) and the median OS from registration was 30.2months (95{\%} CI 9.4, 57.1) for all patients. Seven (33{\%}) patients survived for at least 4.5years, while five (24{\%}) survived for more than 5years, including 2 patients who remain progression-free with durable responses for more than 5years 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. Clinical Trial Registry: NCT00678119",
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TY - JOUR

T1 - Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC)

T2 - Phase 2 study results

AU - Amin, Asim

AU - Dudek, Arkadiusz Z.

AU - Logan, Theodore

AU - Lance, Raymond S.

AU - Holzbeierlein, Jeffrey M.

AU - Knox, Jennifer J.

AU - Master, Viraj A.

AU - Pal, Sumanta K.

AU - Miller, Wilson H.

AU - Karsh, Lawrence I.

AU - Tcherepanova, Irina Y.

AU - DeBenedette, Mark A.

AU - Williams, W. Lee

AU - Plessinger, Douglas C.

AU - Nicolette, Charles A.

AU - Figlin, Robert A.

PY - 2015/4/21

Y1 - 2015/4/21

N2 - 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 (4weeks on, 2weeks off per 6weekcycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3weeks for 5 doses, then every 12weeks 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 11.2months (95% CI 6.0, 19.4) and the median OS from registration was 30.2months (95% CI 9.4, 57.1) for all patients. Seven (33%) patients survived for at least 4.5years, while five (24%) survived for more than 5years, including 2 patients who remain progression-free with durable responses for more than 5years 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. Clinical Trial Registry: NCT00678119

AB - 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 (4weeks on, 2weeks off per 6weekcycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3weeks for 5 doses, then every 12weeks 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 11.2months (95% CI 6.0, 19.4) and the median OS from registration was 30.2months (95% CI 9.4, 57.1) for all patients. Seven (33%) patients survived for at least 4.5years, while five (24%) survived for more than 5years, including 2 patients who remain progression-free with durable responses for more than 5years 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. Clinical Trial Registry: NCT00678119

KW - AGS-003

KW - Dendritic cell

KW - Immunotherapy

KW - RCC

KW - Sunitinib

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U2 - 10.1186/s40425-015-0055-3

DO - 10.1186/s40425-015-0055-3

M3 - Article

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VL - 3

JO - Journal for ImmunoTherapy of Cancer

JF - Journal for ImmunoTherapy of Cancer

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