This is a study of drug KB004 in patients with recurrent glioblastoma (GBM). Eligible
patients with measurable tumours will receive an initial trace (5mg) dose of zirconium
labelled KB004 (89ZrKB004) on day 1 followed by sequential Positron emission tomography (PET)
imaging over 1 week to determine its biodistribution into GBM and normal tissues. Safety
assessments and pharmacokinetic (movement of drug) sampling will also be undertaken over this
time. On Day 8, patients commence weekly KB004 infusions over 2 hours with standard
premedications. Three cohorts are planned in this study (3.5mg/kg, 5.25 mg/kg, 7.9 mg/kg;
additional dose levels may be explored based on toxicity, efficacy and biodistribution data
as determined by the safety monitoring committee). On day 36, patients receive both 89ZrKB004
and KB004, allowing assessment of receptor occupancy to guide recommended phase two dose
(RPTD) determination. Response rate (RANO) and survival data will be collected and patients
benefiting may continue KB004 treatment until disease progression. Primary objective: to
determine the toxicity and recommended phase two dose (RPTD) of KB004 in patients with
advanced Glioblastoma (GBM).
Secondary objectives: to determine the biodistribution and pharmacokinetics of 89ZrKB004; to
determine frequency of EphA3 (ephrin receptor A3) positive glioblastoma in archival specimens
and by 89ZrKB004 scans, and correlate with known biomarkers; to describe response rates per
RANO criteria (Response Assessment in Neuro-Oncology Criteria) and pharmacodynamics following
KB004 infusion; Exploratory objectives: to perform exploratory analysis between clinical
outcomes and biodistribution/Pharmacokinetics (PK)/pharmacodynamics (PD) data, including from
matched biopsies.