ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 60 citations in OpenAlex.
- Randomized Phase II Trial of Capecitabine and Lapatinib with or without IMC-A12 (Cituxumumab) in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab and Chemotherapy: NCCTG N0733 (Alliance).Breast cancer research and treatment · 2021Trial
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- From renal development to pathology: An analysis of the multilevel role of insulin‑like growth factor 2 (Review).Molecular medicine reports · 2026Review
- Cancer-associated fibroblasts: multidimensional players in liver cancer.Frontiers in oncology · 2025Review
- Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection.Epigenetics · 2024Article
- Non-genetic heterogeneity and immune subtyping in breast cancer: Implications for immunotherapy and targeted therapeutics.Translational oncology · 2024Article
- Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer.International journal of molecular sciences · 2024Review
- Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.Biomedicines · 2024Review
- Insulin receptor alternative splicing in breast and prostate cancer.Cancer cell international · 2024Review
- Nephrotoxicity in Bispecific Antibodies Recipients: Focus on T-Cell-Engaging Bispecific Antibodies.OncoTargets and therapy · 2024Review
- Emerging Role of IGF-1 in Prostate Cancer: A Promising Biomarker and Therapeutic Target.Cancers · 2023Review
- The Insulin-like Growth Factor Signaling Pathway in Breast Cancer: An Elusive Therapeutic Target.Life (Basel, Switzerland) · 2022Review
- Mini Review: Molecular Interpretation of the IGF/IGF-1R Axis in Cancer Treatment and Stem Cells-Based Therapy in Regenerative Medicine.International journal of molecular sciences · 2022Review
- Dual Inhibition of EGFR and IGF-1R Signaling Leads to Enhanced Antitumor Efficacy against Esophageal Squamous Cancer.International journal of molecular sciences · 2022Article
- Targeting the IGF/PI3K/mTOR pathway and AXL/YAP1/TAZ pathways in primary bone cancer.Journal of bone oncology · 2022Article
- A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors.Cancer science · 2022Article
- Molecular targets and therapeutics in chemoresistance of triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2021Review
- Review
- Targeting obesity-related dysfunction in hormonally driven cancers.British journal of cancer · 2021Review
Corrections and comments
- Erratum issuedHuang, Jaiqi [corrected to Huang, Jiaqi]
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThis phase I, multicenter, open-label, single-arm, dose-escalation, and dose-expansion study evaluated the safety, tolerability, and antitumor activity of MEDI-573 in adults with advanced solid tumors refractory to standard therapy or for which no standard therapy exists. EXPERIMENTAL
designPatients received MEDI-573 in 1 of 5 cohorts (0.5, 1.5, 5, 10, or 15 mg/kg) dosed weekly or 1 of 2 cohorts (30 or 45 mg/kg) dosed every 3 weeks. Primary end points included the MEDI-573 safety profile, maximum tolerated dose (MTD), and optimal biologic dose (OBD). Secondary end points included MEDI-573 pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor activity.
resultsIn total, 43 patients (20 with urothelial cancer) received MEDI-573. No dose-limiting toxicities were identified, and only 1 patient experienced hyperglycemia related to treatment. Elevations in levels of insulin and/or growth hormone were not observed. Adverse events observed in >10% of patients included fatigue, anorexia, nausea, diarrhea, and anemia. PK evaluation demonstrated that levels of MEDI-573 increased with dose at all dose levels tested. At doses >5 mg/kg, circulating levels of insulin-like growth factor (IGF)-I and IGFII were fully suppressed. Of 39 patients evaluable for response, none experienced partial or complete response and 13 had stable disease as best response.
conclusionsThe MTD of MEDI-573 was not reached. The OBD was 5 mg/kg weekly or 30 or 45 mg/kg every 3 weeks. MEDI-573 showed preliminary antitumor activity in a heavily pretreated population and had a favorable tolerability profile, with no notable perturbations in metabolic homeostasis.
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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.