@article{b09f92c50abc432da2b8986e9f533b01,
title = "Tumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin",
abstract = "Background: The adverse impact of increasing brain tumor size on the efficacy of antibody-drug conjugates (ADCs) was investigated preclinically then validated with clinical data. Methods-Preclinical study: 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. Methods-Clinical study: 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. Results: 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 (\textasciitilde{}98 mm3) versus those with larger volumes (\textasciitilde{}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. Conclusion: 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.",
keywords = "depatuxizumab mafadotin, GBM, tumor volume",
author = "Gan, \{Hui K.\} and Sagun Parakh and Lassman, \{Andrew B.\} and Aidan Seow and Eddie Lau and Lee, \{Sze Ting\} and Malaka Ameratunga and Yuliya Perchyonok and Diana Cao and Burvenich, \{Ingrid J.G.\} and O'keefe, \{Graeme J.\} and Angela Rigopoulos and Erica Gomez and David Maag and Scott, \{Andrew M.\}",
note = "Funding Information: We would like to acknowledge Dr FT Lee and Ms Nancy Guo for their assistance with the production of Zr-Depatux-M and the control antibodies. We also acknowledge Ho-Jin Lee, from Abbvie Inc, for his scientific contribution. We would also like to acknowledge our funding sources including Abbvie for the support of the M12-356 trial; the Cancer Council Victoria (grant No 1164229), the Victorian Cancer Agency (CRE in Brain Cancer), the Operational Infrastructure Support from the Victorian Government, and the Australian Cancer Research Foundation for providing funds to purchase the nanoPET/MRI imaging equipment. This research was also undertaken using the Solid Target Laboratory, an ANSTO-Austin-LICR-ONJCRI Partnership. The support of SP (La Trobe University PhD Scholarship) and AMS (National Health and Medical Research Council Investigator Fellowship No 1177837), the National Cancer Institute/National Institutes of Health (UM1 CA189960 and P30CA013696) and the Rhodes Center for Glioblastoma at New York-Presbyterian Hospital is acknowledged. IJGB is supported by a National Imaging Facility Fellowship. 89 Funding Information: Conflict of interest statement . H.G. has had consulting roles and research funding with AbbVie; speakers bureau and travel support from Ignyta, honoraria from Merck, BMS and Eisai. D.M., H.-J.L., E.G. are full-time employees of AbbVie and may own stock. A.M.S. has consulting roles and research funding from EMD Serono, Abbvie, Astra Zeneca, Telix, Medimmune; he is consultant to Life Science Pharmaceuticals; he has patents on mAb806. A.B.L. (last 2 years) had honoraria and associated travel support from Novocure, Karyopharm, Sapience, Abbott, QED, Society for Neuro-Oncology, Italian Foundation For Cancer Research, Forma, Bayer, Orbus, Bioclinica as an expert blinded independent reviewer of clinical and imaging data for a BMS-sponsored trial, NW Bio, ASCO, AbbVie, Physicians{\textquoteright} Education Resource/Chemotherapy Foundation Symposium, Agios. Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.",
year = "2021",
month = jan,
doi = "10.1093/noajnl/vdab102",
language = "English",
volume = "3",
journal = "Neuro-Oncology Advances",
issn = "2632-2498",
publisher = "Oxford University Press",
number = "1",
}