Investigational New Drugs

, Volume 33, Issue 1, pp 247–253 | Cite as

Phase 2 study of CT-322, a targeted biologic inhibitor of VEGFR-2 based on a domain of human fibronectin, in recurrent glioblastoma

  • David Schiff
  • Santosh Kesari
  • John de Groot
  • Tom Mikkelsen
  • Jan Drappatz
  • Thomas Coyle
  • Lisa Fichtel
  • Bruce Silver
  • Ian Walters
  • David Reardon


VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the 10th type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an open-label run-in/phase 2 setting to assess its efficacy and safety in recurrent glioblastoma. Eligible patients had 1st, 2nd or 3rd recurrence of glioblastoma with measurable tumor on MRI and no prior anti-angiogenic therapy. The initial CT-322 dose was 1 mg/kg IV weekly, with plans to escalate subsequent patients to 2 mg/kg weekly if tolerated; within each CT-322 dose cohort, patients were randomized to ±irinotecan IV semiweekly. The primary endpoint was 6-month progression-free survival (PFS-6). Sixty-three patients with a median age of 56 were treated, the majority at first recurrence. One-third experienced serious adverse events, of which four were at least possibly related to study treatment (two intracranial hemorrhages and two infusion reactions). Twenty-nine percent of subjects developed treatment-emergent hypertension. The PFS-6 rate in the CT-322 monotherapy groups was 18.6 and 0.0 % in the 1 and 2 mg/kg treatment groups, respectively; results from the 2 mg/kg group indicated that the null hypothesis that PFS-6 ≤12 % could not be rejected. The study was terminated prior to reaching the planned enrollment for all treatment groups because data from the completed CT-322 2 mg/kg monotherapy treatment arm revealed insufficient efficacy. Despite biological activity and a tolerable side effect profile, CT-322 failed to meet the prespecified threshold for efficacy in recurrent glioblastoma.


Glioblastoma Adnectin Anti-angiogenic therapy VEGF receptor Irinotecan 


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • David Schiff
    • 1
  • Santosh Kesari
    • 2
  • John de Groot
    • 3
  • Tom Mikkelsen
    • 4
  • Jan Drappatz
    • 2
  • Thomas Coyle
    • 5
  • Lisa Fichtel
    • 6
  • Bruce Silver
    • 7
  • Ian Walters
    • 8
  • David Reardon
    • 9
  1. 1.University of Virginia Neuro-Oncology CenterCharlottesvilleUSA
  2. 2.Dana-Farber Cancer InstituteBostonUSA
  3. 3.M.D. Anderson Cancer CenterHoustonUSA
  4. 4.Henry Ford HospitalDetroitUSA
  5. 5.State University of New York Upstate Medical UniversitySyracuseUSA
  6. 6.South Texas Oncology and HematologySan AntonioUSA
  7. 7.Adnexus, A BMS R&D CompanyWalthamUSA
  8. 8.Bristol-Myers SquibbWallingfordUSA
  9. 9.Duke UniversityDurhamUSA

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