Investigational New Drugs

, Volume 32, Issue 1, pp 178–187 | Cite as

A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma

  • Jonathan E. RosenbergEmail author
  • Richard M. Bambury
  • Eliezer M. Van Allen
  • Harry A. Drabkin
  • Primo N. LaraJr.
  • Andrea L. Harzstark
  • Nikhil Wagle
  • Robert A. Figlin
  • Gregory W. Smith
  • Levi A. Garraway
  • Toni Choueiri
  • Fredrik Erlandsson
  • Damian A. Laber


Background DNA aptamers represent a novel strategy in anti-cancer medicine. AS1411, a DNA aptamer targeting nucleolin (a protein which is overexpressed in many tumor types), was evaluated in patients with metastatic, clear-cell, renal cell carcinoma (RCC) who had failed treatment with ≥1 prior tyrosine kinase inhibitor. Methods In this phase II, single-arm study, AS1411 was administered at 40 mg/kg/day by continuous intravenous infusion on days 1–4 of a 28-day cycle, for two cycles. Primary endpoint was overall response rate; progression-free survival (PFS) and safety were secondary endpoints. Results 35 patients were enrolled and treated. One patient (2.9 %) had a response to treatment. The response was dramatic (84 % reduction in tumor burden by RECIST 1.0 criteria) and durable (patient remains free of progression 2 years after completing therapy). Whole exome sequencing of this patient’s tumor revealed missense mutations in the mTOR and FGFR2 genes which is of interest because nucleolin is known to upregulate mTOR pathway activity by enhancing AKT1 mRNA translation. No other responses were seen. Thirty-four percent of patients had an AS1411-related adverse event, all of which were mild or moderate. Conclusions AS1411 appears to have minimal activity in unselected patients with metastatic RCC. However, rare, dramatic and durable responses can be observed and toxicity is low. One patient in this study had an excellent response and was found to have FGFR2 and mTOR mutations which will be of interest in future efforts to discover and validate predictive biomarkers of response to nucleolin targeted compounds. DNA aptamers represent a novel way to target cancer cells at a molecular level and continue to be developed with a view to improving treatment and imaging in cancer medicine.


AS1411 Nucleolin Renal cell carcinoma Aptamer 


Disclosure of potential conflicts of interest

Frederik Erlandsson – employee of Antisoma. identifier


Grant support

This study was sponsored by Antisoma Research, Ltd.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jonathan E. Rosenberg
    • 1
    • 2
    • 11
    Email author
  • Richard M. Bambury
    • 2
  • Eliezer M. Van Allen
    • 1
    • 3
  • Harry A. Drabkin
    • 4
  • Primo N. LaraJr.
    • 5
  • Andrea L. Harzstark
    • 6
  • Nikhil Wagle
    • 3
  • Robert A. Figlin
    • 7
  • Gregory W. Smith
    • 8
  • Levi A. Garraway
    • 3
  • Toni Choueiri
    • 1
  • Fredrik Erlandsson
    • 9
  • Damian A. Laber
    • 10
  1. 1.Dana-Farber Cancer Institute/Harvard Medical SchoolBostonUSA
  2. 2.Memorial Sloan Kettering Cancer Center/Weill Cornell Medical CollegeNew YorkUSA
  3. 3.The Broad Institute of MIT and HarvardCambridgeUSA
  4. 4.Medical University of South Carolina (MUSC)CharlestonUSA
  5. 5.University of California, DavisSacramentoUSA
  6. 6.University of California, San Francisco (UCSF)San FranciscoUSA
  7. 7.City of Hope Comprehensive Cancer CenterDuarteUSA
  8. 8.St. Francis HospitalBeech GroveUSA
  9. 9.AstraZeneca R&DMölndalSweden
  10. 10.James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  11. 11.New YorkUSA

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