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Title: Tumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin.
Austin Authors: Gan, Hui K ;Parakh, Sagun ;Lassman, Andrew B;Seow, Aidan;Lau, Eddie ;Lee, Sze Ting ;Ameratunga, Malaka;Perchyonok, Yuliya ;Cao, Diana;Burvenich, Ingrid J G;O'Keefe, Graeme J;Rigopoulos, Angela;Gomez, Erica;Maag, David;Scott, Andrew M 
Affiliation: Research and Development Department, AbbVie Inc., North Chicago, Illinois, USA
Department of Medicine, University of Melbourne, Parkville, Australia
Molecular Imaging and Therapy
Division of Neuro-Oncology, Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, NewYork-Presbyterian Hospital, New York, NY, USA
Department of Medical Oncology, Monash Health, Clayton, Melbourne, Australia
Olivia Newton-John Cancer Research Institute
La Trobe University School of Cancer Medicine, Heidelberg, Melbourne, Australia
Medical Oncology
Issue Date: 3-Aug-2021
Date: 2021-01
Publication information: Neuro-Oncology Advances 2021; 3(1): vdab102
Abstract: The adverse impact of increasing brain tumor size on the efficacy of antibody-drug conjugates (ADCs) was investigated preclinically then validated with clinical data. The impact of tumor size on ADC tumor delivery and treatment response was evaluated in an EGFR-amplified patient-derived glioblastoma (GBM) model following treatment with Depatuxizumab mafadotin (Depatux-M). Biodistribution and imaging studies correlated drug distribution with starting treatment volume and anti-tumor activity. M12-356 was a Phase I study of Depatux-M in patients with GBM. Blinded volumetric analysis of baseline tumor volumes of M12-356 patients was undertaken by two reviewers and results correlated with response and survival. Preclinically, imaging and biodistribution studies showed specific and significantly higher tumor uptake of zirconium-89 labeled Depatux-M (89Zr-Depatux-M) in mice with smaller tumor volume (~98 mm3) versus those with larger volumes (~365 mm3); concordantly, mice with tumor volumes ≤100 mm3 at treatment commencement had significantly better growth inhibition by Depatux-M (93% vs 27%, P < .001) and significantly longer overall survival (P < .0001) compared to tumors ≥400 mm3. Clinically, patients with tumor volumes <25 cm3 had significantly higher response rates (17% vs. 0%, P = .009) and longer overall survival (0.5 vs 0.89 years, P = .001) than tumors above 25 cm3. Both preclinical and clinical data showed intra-tumoral concentration and efficacy of Depatux-m inversely correlated with tumor size. This finding merit further investigation with pretreatment tumor volume as a predictor for response to ADCs, in both gliomas and other solid tumors.
DOI: 10.1093/noajnl/vdab102
ORCID: 0000-0001-7319-8546
Journal: Neuro-Oncology Advances
PubMed URL: 34549181
Type: Journal Article
Subjects: GBM
depatuxizumab mafadotin
tumor volume
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