ArticleBritish journal of cancer2020
Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Dose Escalation Trial of BI 836845 Administered Intravenously Once Every Three Weeks in Patients With Advanced Solid Tumours During Escalation and Weekly in Selected Tumour Types During Expansion, With Repeated Administrations in Patients Showing Clinical Benefit
A Phase I Dose Escalation Trial of Weekly Intravenous Administrations of BI 836845 in Patients With Advanced Solid Cancers With Repeated Administrations in Patients Showing Clinical Benefit
Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer.British journal of cancer · 2023Trial
- XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease.Breast cancer research : BCR · 2023Trial
- A phase Ib/II study of xentuzumab, an IGF-neutralising antibody, combined with exemestane and everolimus in hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer.Breast cancer research : BCR · 2021Trial
- Loss of IGF-1R impairs DNA-PKcs recruitment to chromatin leading to defective end-joining.Molecular oncology · 2026Article
- Convergent IGF2 overexpression in pheochromocytoma/paraganglioma: insights from Beckwith-Wiedemann syndrome.Endocrine-related cancer · 2026Article
- Progress in Designing Cytokine Antagonist Antibodies for Cancer Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Assessing insulin resistance: the triglyceride-glucose index as a predictor of survival in nasopharyngeal carcinoma.Frontiers in physiology · 2025Article
- Case Report: Should IGF-1R targeted therapy be revisited in Ewing sarcoma? a report of long-term complete response and review of the literature.Frontiers in oncology · 2025Article
- Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer.Cancers · 2024Review
- Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Structural Models for a Series of Allosteric Inhibitors of IGF1R Kinase.International journal of molecular sciences · 2024Article
- Structural Models for a Series of Allosteric Inhibitors of IGF1R Kinase.bioRxiv : the preprint server for biology · 2024Article
- Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.Biomedicines · 2024Review
- Insulin-like growth factor family and prostate cancer: new insights and emerging opportunities.Frontiers in endocrinology · 2024Review
- IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023Review
- Identification of IGF2 as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma.Molecular cancer therapeutics · 2023Article
- Emerging Role of IGF-1 in Prostate Cancer: A Promising Biomarker and Therapeutic Target.Cancers · 2023Review
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Obesity and endocrine-related cancer: The important role of IGF-1.Frontiers in endocrinology · 2023Review
- Article
Corrections and comments
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Authors and funding
23 authors at 13 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundXentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers.
methodsThese phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]). Primary endpoints were MTD/RBD.
resultsStudy 1280.1 involved 61 patients (part I: xentuzumab 10-1800 mg weekly, n = 48; part II: 1000 mg weekly, n = 13); study 1280.2, 64 patients (part I: 10-3600 mg three-weekly, n = 33; part II: 1000 mg weekly, n = 31). One dose-limiting toxicity occurred; the MTD was not reached for either schedule. Adverse events were generally grade 1/2, mostly gastrointestinal. Xentuzumab showed dose-proportional pharmacokinetics. Total plasma IGF-1 increased dose dependently, plateauing at ~1000 mg/week; at ≥450 mg/week, IGF bioactivity was almost undetectable. Two partial responses occurred (poorly differentiated nasopharyngeal carcinoma and peripheral primitive neuroectodermal tumour). Integration of biomarker and response data by Bayesian Logistic Regression Modeling (BLRM) confirmed the RBD.
conclusionsXentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity. CLINICAL
trial registrationNCT01403974; NCT01317420.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.