Phase 2 study of CT322 a targeted biologic inhib

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

Publish Date: 2014/11/13

Volume: 33, Issue: 1, Pages: 247-253

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Abstract

VEGF signaling through VEGFR2 is the major factor in glioblastoma angiogenesis CT322 a pegylated protein engineered from the 10th type III human fibronectin domain binds the VEGFR2 extracellular domain with high specificity and affinity to block VEGFinduced VEGFR2 signaling This study evaluated CT322 in an openlabel runin/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 antiangiogenic therapy The initial CT322 dose was 1 mg/kg IV weekly with plans to escalate subsequent patients to 2 mg/kg weekly if tolerated within each CT322 dose cohort patients were randomized to ±irinotecan IV semiweekly The primary endpoint was 6month progressionfree survival PFS6 Sixtythree patients with a median age of 56 were treated the majority at first recurrence Onethird experienced serious adverse events of which four were at least possibly related to study treatment two intracranial hemorrhages and two infusion reactions Twentynine percent of subjects developed treatmentemergent hypertension The PFS6 rate in the CT322 monotherapy groups was 186 and 00  in the 1 and 2 mg/kg treatment groups respectively results from the 2 mg/kg group indicated that the null hypothesis that PFS6 ≤12  could not be rejected The study was terminated prior to reaching the planned enrollment for all treatment groups because data from the completed CT322 2 mg/kg monotherapy treatment arm revealed insufficient efficacy Despite biological activity and a tolerable side effect profile CT322 failed to meet the prespecified threshold for efficacy in recurrent glioblastoma

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