{"doi":"10.1093/noajnl/vdab102","title":"Tumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin","abstract":"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 (~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. 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.","journal":"Neuro-Oncology Advances","year":2021,"id":193160,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":761004,"name":"Sagun Parakh","orcid":"0000-0003-3891-2489","position":1,"is_corresponding":false},{"id":295742,"name":"Andrew B. Lassman","orcid":"0000-0001-7386-9928","position":2,"is_corresponding":false},{"id":761527,"name":"Aidan Seow","orcid":null,"position":3,"is_corresponding":false},{"id":761005,"name":"Eddie Lau","orcid":"0000-0002-1261-7775","position":4,"is_corresponding":false},{"id":761006,"name":"Sze Ting Lee","orcid":"0000-0001-8641-456X","position":5,"is_corresponding":false},{"id":761007,"name":"Malaka Ameratunga","orcid":"0000-0002-7171-6781","position":6,"is_corresponding":false},{"id":761008,"name":"Yuliya Perchyonok","orcid":"0000-0003-3476-8766","position":7,"is_corresponding":false},{"id":761009,"name":"Diana Cao","orcid":"0000-0002-6083-837X","position":8,"is_corresponding":false},{"id":519292,"name":"Ingrid J.G. Burvenich","orcid":"0000-0001-8384-2403","position":9,"is_corresponding":false},{"id":745323,"name":"Graeme O’Keefe","orcid":null,"position":10,"is_corresponding":false},{"id":519294,"name":"Angela Rigopoulos","orcid":"0009-0006-0811-7731","position":11,"is_corresponding":false},{"id":761528,"name":"Erica Gomez","orcid":null,"position":12,"is_corresponding":false},{"id":761529,"name":"David Maag","orcid":null,"position":13,"is_corresponding":false},{"id":318594,"name":"Andrew M. Scott","orcid":"0000-0002-6656-295X","position":14,"is_corresponding":false},{"id":761003,"name":"Hui Gan","orcid":"0000-0001-7319-8546","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:49:47.463744Z","pmid":"34549181","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}