HG-44: EVALUATION OF ABT-414 IN CHILDREN WITH HIGH GRADE GLIOMA (HGG) AND DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

BACKGROUND: Pediatric HGGs (WHO grade III and IV gliomas) and DIPGs have no adequate therapy and are almost universally fatal. Amplification of the epidermal growth factor receptor (EGFR) gene occurs in about 50% of GBM (WHO grade IV glioma). ABT-414 is an antibody-drug conjugate comprised of an anti-EGFR antibody linked to a microtubule cytotoxin, monomethyl auristatin F (MMAF). It has demonstrated a promising antitumor activity in phase 1 study in adult GBM patients (M12-356, NCT01800695). Due to the rarity of pediatric HGG with EGFR amplification, a nested cohort has been designed within a phase 2 study of ABT-414 in adult patients with EGFR amplified, recurrent GBM (INTELLANCE 2, NCT02343406). METHODS: ≥6 HGG or DIPG patients will be enrolled globally without randomization in this nested pediatric cohort. Eligible patients will be 3-17 years of age, with recurrent pediatric HGG or DIPG exhibiting EGFR gene 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 ABT-414 every other week intravenously. Primary objectives include evaluating safety, tolerability and pharmacokinetic profile of ABT-414. Since ABT-414 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).