Abstract
BACKGROUND: Depatuxizumab mafodotin (depatux-m, formerly ABT-414), is an antibody-drug conjugate comprised of an EGFR-targeted antibody, a non-cleavable linker maleimidocaproyl, and the microtubule inhibitor monomethylauristatin F. Promising antitumor activity of depatux-m was observed in patients with glioblastoma (GBM) in Phase 12 studies. Dosage of depatux-m is limited by ocular side effects (OSE), such as blurred vision, dry eye, and photophobia from corneal epitheliopathy, which are generally reversible after dose reduction or drug discontinuation. This Phase 3b study evaluates depatux-m-related OSE management strategies used in depatux-m clinical trials. METHODS: This open-label study will enroll approximately 90 patients with newly diagnosed, histologically confirmed, grade IV GBM that is epidermal growth factor receptor (EGFR)-amplified. Patients will receive depatux-m during the chemoradiation phase (radiation and temozolomide [TMZ]), and during adjuvant therapy with TMZ. Patients are randomized to one of three prophylactic ocular treatments: standard steroids (SS), SS with vasoconstrictors and cold compress (VC), or enhanced steroids (ES) with VC. Primary objective is to evaluate these prophylactic strategies for their effect on the proportion of patients requiring a change in OSE management due to inadequate control of OSEs, defined as either a 3-line decline in visual acuity from baseline or Grade 3 OSE severity on the Corneal Epithelial Adverse Event (CEAE) activities of daily living-based scale. Inadequate control with initial prophylactic regimen will trigger a switch to the addition of bandage contact lenses (BCL). Secondary objective assesses change in OSE management due to inadequate control of OSEs by BCL, defined as percentage of patients with Grade 3 CEAE that will trigger transition of patient to investigator discretion regimen (depatux-m interruption/dose reduction, VC prophylaxis, or ES prophylaxis). ClinicalTrials.gov: NCT03419403.