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dc.contributor.authorGan, Hui K-
dc.contributor.authorParakh, Sagun-
dc.contributor.authorLassman, Andrew B-
dc.contributor.authorSeow, Aidan-
dc.contributor.authorLau, Eddie-
dc.contributor.authorLee, Sze Ting-
dc.contributor.authorAmeratunga, Malaka-
dc.contributor.authorPerchyonok, Yuliya-
dc.contributor.authorCao, Diana-
dc.contributor.authorBurvenich, Ingrid J G-
dc.contributor.authorO'Keefe, Graeme J-
dc.contributor.authorRigopoulos, Angela-
dc.contributor.authorGomez, Erica-
dc.contributor.authorMaag, David-
dc.contributor.authorScott, Andrew M-
dc.identifier.citationNeuro-Oncology Advances 2021; 3(1): vdab102en
dc.description.abstractThe 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.en
dc.subjectdepatuxizumab mafadotinen
dc.subjecttumor volumeen
dc.titleTumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin.en
dc.typeJournal Articleen
dc.identifier.journaltitleNeuro-Oncology Advancesen
dc.identifier.affiliationResearch and Development Department, AbbVie Inc., North Chicago, Illinois, USAen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Parkville, Australiaen
dc.identifier.affiliationMolecular Imaging and Therapyen
dc.identifier.affiliationDivision 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, USAen
dc.identifier.affiliationDepartment of Medical Oncology, Monash Health, Clayton, Melbourne, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationLa Trobe University School of Cancer Medicine, Heidelberg, Melbourne, Australiaen
dc.identifier.affiliationMedical Oncologyen
dc.identifier.pubmedid34549181, Hui K
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.openairecristype Oncology- Newton-John Cancer Wellness and Research Centre- Oncology- Imaging and Therapy- Imaging and Therapy- Newton-John Cancer Research Institute-
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