ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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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.
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Who cites it
124 citing papers in PubMed, 230 citations in OpenAlex.
- Trial
- Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma.Investigational new drugs · 2020Trial
- A Phase 2 Study of Galunisertib (TGF-β1 Receptor Type I Inhibitor) and Sorafenib in Patients With Advanced Hepatocellular Carcinoma.Clinical and translational gastroenterology · 2019Trial
- Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine.International journal of molecular sciences · 2017Trial
- A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma.Neuro-oncology · 2016Trial
- Trial
- Inhibiting muscle degeneration in rotator cuff tears: integrative biologic approaches targeting regeneration, fibrosis, and metabolism.Stem cells translational medicine · 2026Review
- TGF-β Signaling as a Pathological Continuum Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Cells · 2026Review
- A preserved TGFβ cytostatic response through DLD-mediated metabolic modulation undermines anti-TGFβ therapy in gastric cancer.Nature communications · 2025Article
- Review
- Dual aVß8 Integrin and PD-1 Blockade Overcomes TGFβ-Mediated B-Cell Suppression to Enhance Anti-Tumor Immunity.Neuro-oncology · 2025Article
- Role of the TGF‑β/Smad signaling pathway in the transition from acute kidney injury to chronic kidney disease (Review).International journal of molecular medicine · 2025Review
- Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response.Nature reviews. Cancer · 2025Review
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- TGFβ-dependent signaling drives tumor growth and aberrant extracellular matrix dynamics in NF1-associated plexiform neurofibroma.Science advances · 2025Article
- IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.Neuro-oncology · 2024Article
- Oncolytic adenovirus encoding decorin and CD40 ligand inhibits tumor growth and liver metastasis via immune activation in murine colorectal tumor model.Molecular biomedicine · 2024Article
- Multifactoral immune modulation potentiates durable remission in multiple models of aggressive malignancy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- The role of stromal cells in epithelial-mesenchymal plasticity and its therapeutic potential.Discover oncology · 2024Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeTGFβ signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGFβ signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a first-in-human dose (FHD) study in patients with cancer. EXPERIMENTAL
designSixty-five patients (58 with glioma) with measurable and progressive malignancies were enrolled. Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28-day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). Safety was assessed using Common Terminology Criteria for Adverse Events version 3.0, echocardiography/Doppler imaging, serum troponin I, and brain natriuretic peptide (BNP) levels. Antitumor activity was assessed by RECIST and Macdonald criteria.
resultsIn part A, 16.6% (5/30) and in part B, 7.7% (2/26) of evaluable patients with glioma had either a complete (CR) or a partial response (PR). In both parts, 15 patients with glioma had stable disease (SD), 5 of whom had SD ≥ 6 cycles of treatment. Therefore, clinical benefit (CR+PR+SD ≥ 6 cycles) was observed in 12 of 56 patients with glioma (21.4%). LY2157299 was safe, with no cardiac adverse events.
conclusionsOn the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation.
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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.