Pharmacokinetics, pharmacodynamics, safety and tolerability of APG101, a CD95-Fc fusion protein, in healthy volunteers and two glioma patients

Int Immunopharmacol. 2012 May;13(1):93-100. doi: 10.1016/j.intimp.2012.03.004. Epub 2012 Mar 21.


APG101 is a glycosylated fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of human IgG1. Administration of APG101 blocks the interaction between CD95 and its cognate ligand CD95L, thereby inhibiting various pathways involved in e.g. proliferation, migration, differentiation and apoptosis induction. The safety and tolerability of ascending single doses of intravenously applied APG101 was examined in a randomized, double-blind, placebo-controlled, mono-centre "first in man" dose escalation study in 34 healthy male volunteers. Pharmacokinetics and pharmacodynamics were also assessed. The maximum serum concentration of 460 μg/ml was achieved following 1h infusion of the highest dose of 20 mg/kg. The systemic clearance was low (0.4 to 0.5 ml/hkg). Mean terminal elimination half-life was 12 to 15 days. Two patients suffering from malignant glioma received APG101 intravenously under compassionate use conditions. They received doses ranging from 5mg to 600 mg APG101. No adverse events and no clinical significant changes in laboratory parameters related to APG101 were reported. The presence of anti-drug-antibodies (ADA) was investigated and revealed no detectable levels of ADA. Overall, single ascending doses of APG101 up to 20 mg/kgbody weight (bw) administered as infusion over 1h were considered as safe and well tolerated in healthy volunteers. After the application of multiple doses of 400 mg in two glioma patients, steady state for APG101 seemed to be reached. These results support further clinical evaluation of APG101 at a dose of 400 mg per week in glioblastoma patients.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Brain Neoplasms / blood
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Compassionate Use Trials
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Glioma / blood
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Immunoglobulin Fc Fragments / adverse effects
  • Immunoglobulin Fc Fragments / blood
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / blood
  • Immunoglobulin G / therapeutic use*
  • Infusions, Intravenous
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / blood
  • Recombinant Fusion Proteins / therapeutic use*
  • Young Adult
  • fas Receptor / adverse effects
  • fas Receptor / blood
  • fas Receptor / therapeutic use*


  • Antineoplastic Agents
  • FAS protein, human
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • fas Receptor
  • APG101