OS07.4 Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, as monotherapy in epidermal growth factor receptor (EGFR) amplified (EGFRamp), recurrent glioblastoma (rGBM)
Year: 2017
Type: article
Study design: Clinical Trial
Abstract: Background: Patients (pts) with rGBM have a poor prognosis. EGFRamp is present in ~50% of GBMs. ABT-414 is an ADC that releases a potent toxin, monomethyl auristatin F (MMAF), inside cells with EGFRamp. Here we report the safety and efficacy of ABT-414 monotherapy at the recommended phase 2 dose (RPTD) in EGFRamp, rGBM. Methods: M12-356 (NCT01800695) is an open-label, Phase 1 study with three escalation cohorts. Study design and RPTD was reported previously (ASCO Meeting 2015, SNO Meeting 2015). Sixty pts, all with EGFRamp, rGBM, were enrolled as part of the escalation (12 pts) or expansion (48 pts) cohort treated with ABT-414 monotherapy at 1.25 mg/kg. Adults with measurable (RANO), bevacizumab-naïve, rGBMs with EGFRamp confirmed centrally were eligible. Results: As of March 1, 2016, 60 pts with EGFRamp, rGBM underwent treatment. Median age was 58 years (range, 35–80). Pts underwent 1, 2 (43% each) or 3 (13%) prior therapies. The most common treatment emergent adverse events (TEAEs) (≥20% pts) included blurred vision (65%), headache, fatigue (30% each), eye pain and photophobia (28% each). Grade 3/4 TEAEs (>1 pt) were keratitis (13%), corneal epithelial microcysts (8%), blurred vision (5%), dry eye, ulcerative keratitis and reduced visual acuity (3% each). The best RANO responses of 56 pts with complete data were: 3 (5%) partial responses, 24 (43%) stable diseases and 29 (52%) progressive diseases. Median duration of overall response in 3 patients with partial responses was 4.4 months (range, 1.9–5.6). The 6-month progression-free survival (PFS6) estimate was 25.3% [95% CI=14.8, 37.2]. Conclusions: ABT-414 monotherapy displayed frequent but mostly grade 1/2 ocular toxicities. An encouraging PFS6 (25%) was observed in this rGBM population where 56% had ≥2 prior therapies. A global randomized trial of ABT-414, alone or with TMZ, vs. TMZ or lomustine, is underway in EGFRamp, rGBM (NCT02343406).
Source: Neuro-Oncology
Institutions: Erasmus MC, Erasmus MC Cancer Institute, Austin Health, Olivia Newton-John Cancer Research Institute, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, Northwestern University, University of California System, University of Alabama at Birmingham, National Health and Medical Research Council, AbbVie (United States), Dana-Farber Cancer Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4251819462