depatuxizumab (ABT-806) / AbbVie, Life Science Pharma - LARVOL DELTA

Multimodal cancer therapy consisting of antibody-drug conjugates and radiotherapy in cancer treatment (AACR 2025) - "Accordingly, combination of RT with ADCs targeting HER2: trastuzumab emtansine/deruxtecan/duocarmazine (T-DM1/T-DXd/T-Duo) and disitamab vedotin, TROP2: datopotamab deruxtecan and sacituzumab govitecan, EGFR: depatuxizumab MMAE, HER3: patritumab deruxtecan, Nectin4: enfortumab vedotin and CEACAM5: tusamitamab ravtansine were evaluated. Together, this study demonstrates that inherent sensitivity of tumor cells to different payload classes, DAR and TAA dynamic are of relevance for the efficacy of ADC. Informed selection of ADC exhibited synergistic effects with RT providing a novel multimodal and promising strategy for efficient cancer eradication."

Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • EGFR • ERBB3 • HER-2 • NECTIN4

Design of immunogens to present a tumor-specific cryptic epitope. (PubMed, Sci Rep) - "Two mutants in which the epitope remained stable in subsequent simulations were chosen for evaluation in vitro. Binding kinetics experiments with these designed immunogens provided strong evidence that the epitope was successfully stabilized in the mAb806-binding conformation, suggesting that they could potentially form the basis of vaccines that elicit cancer-selective antibodies."

Journal • Oncology • EGFR

Locoregional Infusion of EGFR806-CAR T Cells for Recurrent or Refractory Pediatric CNS Tumors: Results of the Completed BrainChild02 Phase 1 Clinical Trial. (PubMed, Neuro Oncol) - "Intracranially infused EGFR806-CAR T cells were tolerable at tested doses, with a best response of stable disease. EGFR is a potentially useful target for cellular therapy against pediatric brain tumors, particularly high-grade gliomas."

Journal • P1 data • Brain Cancer • CNS Disorders • CNS Tumor • Diffuse Midline Glioma • Epilepsy • Glioma • Malignant Glioma • Oncology • Pain • Pediatrics • Rhabdoid Tumor • Sarcoma • Solid Tumor • EGFR

Tumour volumes predict prognosis and response to treatment with Depatuxizumab Mafadotin (SNO 2024) - "We investigated the impact of tumor volumes on outcomes with Depatux-M in the EORTC randomized phase 2 Intellance 2 study on recurrent glioblastoma (NeuroOncol 22(5):684). 260 patients were randomized to Depatux-M, Depatux-M with temozolomide, or control treatment (lomustine/temozolomide). Tumor volumes are an important prognostic variable in recurrent glioblastoma and modulate survival to large molecules like Depatux-M."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Radiolabeling and Preclinical Evaluation of Therapeutic Efficacy of 225Ac-ch806 in Glioblastoma and Colorectal Cancer Xenograft Models. (PubMed, J Nucl Med) - " In glioblastoma and colorectal tumor models, 225Ac-ch806 significantly inhibited tumor growth via induction of double-strand breaks, thereby constraining cancer cell proliferation while inducing cell cycle arrest and apoptosis. These findings underscore the potential clinical applicability of 225Ac-ch806 as a potential therapy for EGFR-expressing solid tumors."

Journal • Preclinical • Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Solid Tumor • CASP3 • CDKN1A

An anion exchange membrane sensor detects EGFR and its activity state in plasma CD63 extracellular vesicles from patients with glioblastoma. (PubMed, Commun Biol) - "Notably, we target both total and "active" EGFR on EVs; with a monoclonal antibody mAb806 that recognizes a normally hidden epitope on overexpressed or mutant variant III EGFR. Analysis of samples yielded an area-under-the-curve (AUC) value of 0.99 and a low p-value of 0.000033, surpassing the performance of existing assays and markers."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD63 • EGFR

Focus on current and emerging treatment options for glioma: A comprehensive review. (PubMed, World J Clin Oncol) - "This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev...Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms...In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Pediatrics • Solid Tumor

Patients with EGFR amplification but without EGFRvIII expression have improved benefit compared to those with EGFRvIII expression in samples of the INTELLANCE2/EORTC1410 randomized phase II trial (AACR 2019) - "Background: Depatux-M (ABT-414) is an antibody-drug-conjugate consisting of an antibody (ABT-806) bound to the toxin monomethylauristatin-F. Depatux-M in combination with TMZ showed a trend towards improved OS in EGFR amplified recurrent glioblastoma. This trend may be greater for subjects with an absence of EGFRvIII expression."

Clinical • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

TUMOR VOLUME AS A PREDICTOR OF RESPONSE TO ANTI-EGFR ADC ABT-414 (SNO 2018) - P1; "...The tumour-specific anti-EGFR ADC, depatuxizumab mafadotin (depatux-m), demonstrated encouraging activity in a Phase 1 glioblastoma study (M12-356 study, NCT01800695)...110 patients with EGFR-amplified, recurrent glioblastoma were treated with depatux-m, alone or in combination with temozolomide... Increased tumour volumes results in significant reduction in ADC penetration. The impact of this as a modifiable factor, within the broader prognostic impact of increased tumour volume, warrants further investigation with prospective and/or randomized data."

Brain Cancer • Oncology • Solid Tumor

TWO-YEAR RESULTS OF THE INTELLANCE 2/EORTC TRIAL 1410 RANDOMIZED PHASE II STUDY ON DEPATUX–M ALONE, DEPATUX-M COMBINED WITH TEMOZOLOMIDE (TMZ) AND EITHER TMZ OR LOMUSTINE IN RECURRENT EGFR AMPLIFIED GLIOBLASTOMA (NCT02343406 (SNO 2018) - P2; "BACKGROUND:Depatux-M is an antibody-drug-conjugate consisting of an antibody (ABT-806) specific to the activated conformation of EGFR bound to the toxin monomethylauristatin-F. This updated OS analysis of Depatux-M in combination with temozolomide confirmed the OS improvement in EGFRamp recurrent glioblastoma. In Depatux-M treated patients, higher drug levels during course 1 were associated with improved OS, but high levels of EGFR amplification at first diagnosis were not."

Clinical • P2 data • Brain Cancer • Oncology • Solid Tumor

Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: Safety, pharmacokinetics, and antitumor activity in advanced glioblastoma. (PubMed, Neurooncol Adv) - P1 | "Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. Ser-T monotherapy at doses up to 50 μg/kg initial dose, followed by 25 μg/kg Q4W demonstrated a tolerable safety profile with minimal antitumor activity observed in patients with glioblastoma. The glioblastoma dose-expansion cohort was closed due to a lack of efficacy (NCT03234712)."

Journal • Metastases • P1 data • PK/PD data • Brain Cancer • CNS Tumor • Dermatology • Fatigue • Glioblastoma • Oncology • Pruritus • Solid Tumor • EGFR

[VIRTUAL] High affinity chimeric antigen receptor with cross-reactivity to clinically-relevant EGFR mutated proteins (SNO 2020) - P1 | "To study this further We generated two structurally different CARs by fusing the scFv of mAb806 to 4-1BB and Killer immunoglobulin like receptor (KIR) co-stimulatory domains...Unlike EGFR-specific cetuximab based CAR, EGFR-806CART cells did not kill EGFR wild type expressing fetal brain primary astrocytes and keratinocytes in vitro...The broad specificity of EGFR806 CART cells to amplified EGFR and its mutant variants gives us the potential to clear various forms of EGFR. The enhanced anti-tumor efficacy by KIR based CAR in vivo setting provides us with additional therapeutic options."

Clinical • Glioblastoma • Graft versus Host Disease • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • EGFR

Epidermal growth factor receptor (EGFR) amplification rates observed in screening patients for randomized clinical trials in glioblastoma (ESMO 2017) - P2,P2b; "Depatuxizumab mafodotin (depatux-m), formerly called ABT-414, is a tumor-specific antibody-drug conjugate that preferentially targets tumors with EGFR amplification. This study represents the first report of lower EGFR amplification rates in patients from Asia with glioblastoma to our knowledge. This observation requires further study."

Clinical • Solid Tumor

Anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma. (ASCO-GI 2017) - P2; "Pts received 1L ABT-806 (1/4) or 2L+ cetux (3/4) monoclonal anti-EGFR antibodies, in combination with chemotherapy if 1L or 2L (2/4), or as monotherapy for 3L+ (2/4). EGFR amp incidence was similar to TCGA. Despite large negative trials with EGFR antagonists for GEC, EGFR amp predicted benefit (100%) from anti-EGFR tx, including monotherapy in 50%, albeit until various resistance mechanisms emerged, including HER2, RAS, and PTEN/AKT pathway activation. No PD-L1 expression was observed pre/post treatment, consistent with our previous data showing that EGFR-amplified cases trend towards a ‘non-T cell-inflamed’ phenotype."

Biomarker • Clinical • Biosimilar • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology

EGFR as a potent CAR T target in triple negative breast cancer brain metastases. (PubMed, Breast Cancer Res Treat) - "Our results demonstrates anti-tumor activity of EGFR806 CAR T cells against TNBC cells in vitro and in vivo. Given EGFR806 CAR T cells are currently undergoing clinical trials in primary brain tumor patients without obvious toxicity, our results are immediately actionable against the TNBC-BM patient population."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EGFR

Biodistribution Analysis of an Anti-EGFR Antibody in the Rat Brain: Validation of CSF Microcirculation as a Viable Pathway to Circumvent the Blood-Brain Barrier for Drug Delivery. (PubMed, Pharmaceutics) - "To pave the way for future efficacy studies for the treatment of GBM with an intra-CSF administered ADC consisting of a conjugate of ABT-806 (or of one of its close analogs), we verified in vivo the binding of ABT-414 to GBM tumor cells implanted in the cisterna magna and collected toxicity data from both the central nervous system (CNS) and peripheral tissues. The current study supports further exploration of harnessing CSF microcirculation as an alternative to systemic delivery to achieve higher brain tissue exposure, while reducing previously reported ocular toxicity with ABT-414."

Journal • Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Oncology • Solid Tumor • EGFR

Investigating the impact of NGS data availability on clinical decision-making in brain cancer. (ASCO 2022) - " Of 44 Astrocytoma patients with potentially actionable mutations, four (9.1%) were treated with targeted therapy in the form of Enasidenib, ONC201, Nivolumab, and Depatuxizumab, while 40 received NGS agnostic treatment. In 37 Oligodendroglioma patients, three (8.1%) were treated with either targeted Vorasidenib or Ivosidenib, while 34 were started on NGS agnostic therapies. Lastly, four (10.0%) of 40 patients with other rare primary tumor types received either Ibrutinib, Dabrafenib+Trametinib, Vigabatrin, or Vemurafenib as targeted therapy. Avastin and/or standard Temozolomide chemotherapy were the most common NGS agnostic therapies employed by clinicians across all three subclasses... Although a substantial number of potentially actionable mutations were detected by NGS, the presence of this data paired with Tempus targeted recommendations rarely impacted clinician decision-making, ranging from 8.1-10.0% of the time. Despite the availability of resources to prescribe..."

Clinical • Next-generation sequencing • Anaplastic Oligoastrocytoma • Astrocytoma • Brain Cancer • CNS Lymphoma • Ependymoma • Glioblastoma • Glioma • Hematological Malignancies • Lymphoma • Meningioma • Oligodendroglioma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor

[VIRTUAL] EGFR inhibition in EGFR-amplified esophagogastric cancer (EGC): Retrospective global experience (ESMO 2021) - "Testing could be by tissue-next generation sequencing (NGS), cell-free DNA (cfDNA)-NGS, or fluorescence in-situ hybridization (FISH) performed by a CLIA-approved laboratory. Fifty-six pts received cetuximab (n=26), ABT-806 (n=13), panitumumab (n=10), gefitinib (n=5), or cetuximab + TKI (n=2), and 29 (52%) patients received concurrent chemotherapy. Pts with EGFR-amplified EGC derive clinical benefit from EGFR inhibition, which is most pronounced in the absence of intrinsic resistance mechanisms. An upcoming trial of amivantamab in EGFR and/or MET amplified EGC is planned."

Retrospective data • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • MET • PIK3CA

Ocular surface toxicity of depatuxizumab mafoditin (ABT-414): case reports. (PubMed, Arq Bras Oftalmol) - "The initiation of artificial tears and lubricant ointment was enough to control the ocular surface signs and symptoms. A multidisciplinary approach, complete ophthalmologic monitorization, and elaboration of protocols are required to adequately manage these patients."

Clinical • Journal • Brain Cancer • Glioblastoma • Keratitis • Ocular Inflammation • Oncology • Ophthalmology • Solid Tumor

Tumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin. (PubMed, Neurooncol Adv) - "The adverse impact of increasing brain tumor size on the efficacy of antibody-drug conjugates (ADCs) was investigated preclinically then validated with clinical data. 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 • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • EGFR

Updated results of the INTELLANCE 2/EORTC trial 1410 randomized phase II study on Depatux M alone, Depatux-M in combination with temozolomide (TMZ) and either TMZ or lomustine (LOM) in recurrent EGFR amplified glioblastoma (NCT02343406). (ASCO 2018) - P2; "NCT02343406 Background: Depatux-M is a tumor-specific antibody-drug-conjugate consisting of an antibody (ABT-806) bound to the toxin monomethylauristatin-F. This updated OS analysis of Depatux-M in combination with TMZ confirmed the OS improvement in EGFRamp recurrent glioblastoma. In Depatux-M treated patients, higher drug levels during course 1 were associated with improved OS but high levels of EGFR amplification at first diagnosis were not."

Clinical • Combination therapy • P2 data • Solid Tumor

Personalized antibodies for gastroesophageal adenocarcinoma (PANGEA): A phase II precision medicine trial (NCT02213289). (ASCO-GI 2018) - P2; "Pts receive first line (1L) mFOLFOX6 + biologic tx based on BP of the ML using a prioritized tx algorithm (HER2+: trastuzumab; MET+: none; FGFR2+: none; EGFR+: ABT806; MSI-H: nivolumab; ‘RAS-like’: ramucirumab). Secondary endpoints include rate of baseline MH between PT and ML leading to new treatment assignment; utility of cfDNA; overall progression-free survival (PFS)/response rate (RR); OS/PFS/RR in each targetable group. Since 8/2015, 38 of 68 planned pts have been accrued."

P2 data • Esophageal Cancer

111In-ch806 in Patients With Advanced Tumours Expressing the 806 Antigen (clinicaltrials.gov) - P1; N=8; Completed; Sponsor: Ludwig Institute for Cancer Research; N=12 ➔ 8

Clinical • Enrollment change • Oncology

PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression (clinicaltrials.gov) - P2; N=80; Completed; Sponsor: University of Chicago; Active, not recruiting ➔ Completed

Trial completion • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2 • PD-1

A Phase 1 and Biodistribution Study of ABT-806i, An Indium-111 Radiolabeled Conjugate of the Tumor-Specific Anti-EGFR Antibody ABT-806. (PubMed, J Nucl Med) - " ABT-806i allows for real-time imaging of EGFR conformational expression in tumors, has an acceptable radiation dosimetry and provides important additional information about antigen expression compared to standard approaches using archival tissue. Its role to assist in patient selection for EGFR-based therapeutics and investigate treatment resistance should be further investigated."

Journal • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • EGFR