Prolonged survival with personalized immunotherapy (AGS-003) in combination with sunitinib in unfavorable risk metastatic RCC (mRCC). Academic Article

abstract

  • 357 Background: During the past decade, VEGF targeted therapies have become standard treatment for advanced RCC. While targeted therapies have yielded improved efficacy, durable remissions are rare, particularly in unfavorable risk subjects. In a pivotal trial, treatment with sunitinib yielded a median OS of 5.3 months for poor risk and 20.7 months for intermediate risk subjects. Similarly, the validation dataset for the Heng risk model (ASCO 2011) revealed a median OS of 8 months for poor risk and 21 months for intermediate risk patients treated with VEGF targeted therapies. Durable responses have been elicited by immunotherapy in RCC. We report an update on patients with mRCC treated with combined VEGF TKI (sunitinib) plus autologous immunotherapy (AGS-003). Methods: In this phase II study, subjects with unfavorable prognosis mRCC (poor and intermediate risk) were treated with sunitinib plus autologous dendritic cell immunotherapy (AGS-003). Treatment consisted of standard 6-week cycles of sunitinib plus AGS-003 (once every 3 weeks x5 doses, then every 12 weeks until PD). Tumor response was assessed per RECIST and subjects were followed for PFS and OS. Immune monitoring samples were taken at screening, baseline and after the third and fifth doses of AGS-003 and analyzed by multiparametric flow cytometry. Results: 21 subjects were treated. As previously reported, the median overall PFS was 11.2 months and the final median OS was 30.2 months. When analyzed by baseline Heng risk status, the median PFS was 19.4 months for intermediate (n=11) and 5.8 months for subjects with poor risk features (n=10) at baseline. The median OS is 39.5+ months for intermediate and 9.1 months for subjects with poor risk. Conclusions: The results from this single-arm phase II study represent a near doubling of expected PFS and OS for unfavorable risk subjects treated with AGS-003 plus sunitinib. Updated survival and immunologic findings will be presented, as 8 of 21 subjects are still alive and continue to be followed. These results support the ongoing phase III ADAPT study, which is designed to validate these encouraging clinical and immunologic findings. Clinical trial information: NCT00678119.

authors

  • Amin, Asim
  • Dudek, Arkadiusz
  • Logan, Theodore
  • Lance, Raymond S.
  • Holzbeierlein, Jeffrey M.
  • Master, Viraj A.
  • Pal, Sumanta Kumar
  • Knox, Jennifer J.
  • Karsh, Lawrence, MD, FACS, CPI
  • Plessinger, Doug
  • Nicolette, Charles A.
  • Figlin, Robert A.

Publication Date

  • 2013

webpage

published in

Digital Object Identifier (DOI)

number of pages

  • 1

start page

  • 357

end page

  • 357

volume

  • 31

issue

  • 6_suppl