Abtc-1701: Pilot surgical pk study of bgb324 (bemcentinib) in recurrent glioblastoma patients-results from interim futility analysis

Document Type

Conference Proceeding

Publication Date

11-12-2021

Publication Title

Neuro Oncol

Keywords

bemcentinib, adult, brain tissue, brain tumor, cancer combination chemotherapy, cancer patient, cancer recurrence, cancer surgery, chemoradiotherapy, clinical article, clinical trial, conference abstract, controlled study, drug therapy, excision, female, glioblastoma, histopathology, human, human tissue, liquid chromatography-mass spectrometry, male, middle aged, monotherapy, multicenter study, oral drug administration, pharmacokinetics, radiotherapy

Abstract

BACKGROUND: Glioblastoma often can relapse as mesenchymal (MES) tumors, indicating a phenotypic shift during clinical progression. Glioma spheres, when they gain MES phenotypes, develop dependence on AXL for their growth both in vitro and in vivo. The first-in-class orally bioavailable AXL kinase inhibitor bemcentinib has IC50 of 14 nM and is > 100-fold selective for AXL over other kinases. Bemcentinib is currently under evaluation as a monotherapy and in combination with other treatments across various PhII trials in several oncology indications. METHODS: This is an open-label, multicenter, intratumoral pharmacokinetic study of bemcentinib in patients with recurrent glioblastoma for whom a surgical resection is medically indicated. All subjects must have had histological confirmation of glioblastoma by either biopsy or resection that is progressive or recurrent following radiation therapy ± chemotherapy. Intratumoral drug levels were analyzed by LC/MS. RESULTS: A planned analysis after the first 5 patients were enrolled with glioblastoma (4 IDH WT and 1 IDH-mutant), (3m, 2f, median age 57, KPS 80). Bemcentinib concentration in contrast enhancing brain tissue ranged from 3.1 to 43.0 uM with a geometric mean concentration of 11.1 uM (% CV, 132.1). The drug concentration in contrast enhancing tumor tissue exceeded the 1.0 uM threshold in all 5 patients, satisfying the criteria of the protocol to enroll an additional 15 patients into the surgical study. Total drug levels were approximately 2-fold greater in contrast enhancing tissue as compared to tissue from a non-enhancing region of the tumor (geometric mean, 5.8 uM; % CV, 187.7). The mean ratio of the drug concentration in brain tissue to plasma was 25.9 (% CV, 92.7) for contrast enhancing tissue and 13.4 (% CV, 126.8) for non-enhancing tissue. CONCLUSIONS: Bemcentinib readily distributes in brain tumor tissue following oral administration. The study continues to complete accrual for the remaining 15 patients.

PubMed ID

Not assigned.

Volume

23

Issue

SUPPL 6

First Page

vi60

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