PDCT-02. EVALUATION OF DEPATUXIZUMAB MAFODOTIN (ABT-414) IN CHILDREN WITH HIGH GRADE GLIOMA (HGG) AND DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Abstract

BACKGROUND: Pediatric HGGs (WHO grade III and IV gliomas) and DIPGs have no adequate therapy and are almost universally fatal. Depatuxizumab mafodotin (depatux-m), formerly called ABT-414, is an antibody-drug conjugate, comprised of an anti-EGFR antibody linked to a microtubule cytotoxin, monomethyl auristatin F (MMAF), that has demonstrated promising antitumor activity in patients with epidermal growth factor receptor (EGFR) gene-amplified tumours in a phase 1 study in adult GBM (M12-356, NCT01800695). While EGFR amplification occurs in about 50% of GBM (WHO grade IV glioma), it occurs in up to 3% only in children with HGG. Due to the rarity of pediatric HGG with EGFR amplification, a nested cohort has been designed within a phase 2 study of depatux-m in adult patients with EGFR amplified, recurrent GBM (INTELLANCE 2, NCT02343406). METHOD(S): >=6 HGG or DIPG patients will be enrolled globally without randomization to receive depatux-m in this nested pediatric cohort. Eligible patients will be 3-17 years of age, with recurrent pediatric HGG or DIPG exhibiting EGFR amplification or EGFRvIII mutation (local or central testing). Patients and/or their legal guardians must sign an informed assent/consent form. Patients will receive either 1.0 mg/kg (6-17 years) or 1.3 mg/kg (3-5 years) of depatux-m every other week intravenously. Primary objectives include evaluating safety, tolerability and pharmacokinetic profile of depatux-m. Since depatux-m displayed frequent, yet reversible, ocular toxicity in adult patients (M12-356 study), ophthalmology examination will be performed throughout the study. The secondary objective will be to determine the tumor response per RANO criteria. Exploratory endpoints include assessing progression- free survival, overall survival, steroid use, and health-related quality of life (HRQOL).