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

Robert A Figlin¹  Charles A Nicolette⁵  Douglas C Plessinger⁵  W Lee Williams⁵  Mark A DeBenedette⁵  Irina Y Tcherepanova⁵  Lawrence I Karsh^1,12  Wilson H Miller⁷  Sumanta K Pal^1,10  Viraj A Master³  Jennifer J Knox⁹  Jeffrey M Holzbeierlein^1,11  Raymond S Lance²  Theodore F Logan⁶  Arkadiusz Z Dudek⁸  Asim Amin⁴ 

[1] Cedars-Sinai Medical Center, Los Angeles, CA, USA;Urology of Virginia, Norfolk, VA, USA;Emory University, Atlanta, GA, USA;Levine Cancer Institute, Charlotte, NC, USA;Argos Therapeutics, Inc., Durham, NC, USA;Indiana University Simon Cancer Center, Indianapolis, IN, USA;Lady Davis Institute and Segal Cancer Center-Jewish General Hospital, McGill University, Montreal, QC, Canada;University of Illinois Cancer Center, Chicago, IL, USA;Princess Margaret Hospital, Toronto, ON, Canada;City of Hope Comprehensive Cancer Center, Duarte, CA, USA;University of Kansas Medical Center, Kansas City, KS, USA;The Urology Center of Colorado, Denver, CO, USA

关键词: Sunitinib;    AGS-003;    RCC;    Dendritic cell;    Immunotherapy;   

Others  :  1204147
DOI  :  10.1186/s40425-015-0055-3

 received in 2014-10-06, accepted in 2015-03-02,  发布年份 2015

【 摘 要 】

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.

Clinical Trial Registry

#NCT00678119 webcite

【 授权许可】

   
2015 Amin et al.; licensee BioMed Central.

【 图 表 】

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