ArticleInvestigational new drugs2016
A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies.
Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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Who cites it
46 citing papers in PubMed, 60 citations in OpenAlex.
- Synergistic Regulation of Tumor Immunity by Integrins and Lectins: From Molecular Mechanisms to Dual-Targeted Therapy.International journal of molecular sciences · 2026Review
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- ITGAV and SMAD4 influence the progression and clinical outcome of pancreatic ductal adenocarcinoma.Molecular oncology · 2025Article
- The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer.Journal of translational medicine · 2025Article
- An FDA-approved drug library screening identifies proteasome inhibitors as selective cytotoxic agents for angiosarcoma cells.British journal of cancer · 2025Review
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Integrin-α5 expression and its role in non-small cell lung cancer progression.Cancer science · 2025Article
- Integrin β1 in breast cancer: mechanisms of progression and therapy.Breast cancer (Tokyo, Japan) · 2025Review
- Integrin signaling in tumor biology: mechanisms of intercellular crosstalk and emerging targeted therapies.PeerJ · 2025Review
- Cilengitide sensitivity is predicted by overall integrin expression in breast cancer.Breast cancer research : BCR · 2024Article
- Galectin 3-binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1 (TGF-β1) availability and inhibits hepatocarcinogenesis.Cancer communications (London, England) · 2024Article
- SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications.Molecular cancer therapeutics · 2023Article
- Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2023Review
- Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams.Cancers · 2023Review
- Lineage-Specific Induced Pluripotent Stem Cell-Derived Smooth Muscle Cell Modeling Predicts Integrin Alpha-V Antagonism Reduces Aortic Root Aneurysm Formation in Marfan Syndrome Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Broad spectrum integrin inhibitor GLPG-0187 bypasses immune evasion in colorectal cancer by TGF-β signaling mediated downregulation of PD-L1.American journal of cancer research · 2023Article
- Pan-integrin inhibitor GLPG-0187 promotes T-cell killing of mismatch repair-deficient colorectal cancer cells by suppression of SMAD/TGF-β signaling.American journal of cancer research · 2023Article
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin binding.JCI insight · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntegrin signaling is an attractive target for anti-cancer treatment. GLPG0187 is a broad spectrum integrin receptor antagonist (IRA). GLPG0187 inhibited tumor growth and metastasis in mouse models.
methodsWe aimed to determine the Recommended Phase II Dose (RP2D) and to assess safety and tolerability of continuous i.v. infusion in patients with advanced malignant solid tumors. Anticipated dose levels were 20, 40, 80, 160, 320, and 400 mg/day in a modified 3 + 3 design. Plasma concentrations of GLPG0187 were assessed to characterize the pharmacokinetics (PK). C-terminal telopeptide of type I collagen (CTX) was used as pharmacodynamics marker.
resultsTwenty patients received GLPG0187. No dose limiting toxicities (DLTs) were observed. The highest possible and tested dose was 400 mg/day. Fatigue was the most frequently reported side effect (25%). Recurrent Port-A-Cath-related infections and skin toxicity suggest cutaneous integrin inhibition. No dose-dependent toxicity could be established. PK analysis showed a short average distribution (0.16 h) and elimination (3.8 h) half-life. Continuous infusion resulted in dose proportional PK profiles. We observed decreases in serum CTX levels independent of the dose given, suggesting target engagement at the lowest dose level tested. Single agent treatment did not result in tumor responses.
conclusionsGLPG0187 was well tolerated with a dose-proportional PK profile upon continuous infusion. No formal maximal tolerated dose could be established. GLPG0187 showed signs of target engagement with a favourable toxicity profile. However, continuous infusion of GLPG0187 failed to show signs of monotherapy efficacy.
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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.