A5020397401- TGF-β signaling in diseases
- Pancreatic and Hepatic Oncology Research
- Statistical Methods in Clinical Trials
- Glioma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Alzheimer's disease research and treatments
- Renal cell carcinoma treatment
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- Optimal Experimental Design Methods
- Pharmacogenetics and Drug Metabolism
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Analytical Chemistry and Chromatography
- Dementia and Cognitive Impairment Research
- Cancer Immunotherapy and Biomarkers
- Drug Transport and Resistance Mechanisms
- Cancer Cells and Metastasis
- Chronic Myeloid Leukemia Treatments
- Computational Drug Discovery Methods
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Treatment and Pharmacology
- Analytical Methods in Pharmaceuticals
Eli Lilly (United Kingdom)
2015-2025
Eli Lilly (United States)
2014-2025
Institute of Neurological Sciences
2016
University Hospital Heidelberg
2016
Goethe University Frankfurt
2016
Université Sorbonne Paris Nord
2016
Royal North Shore Hospital
2016
Hôpital Avicenne
2016
Heidelberg University
2016
Digital Catapult
2013
The combination of galunisertib, a transforming growth factor (TGF)-β receptor (R)1 kinase inhibitor, and lomustine was found to have antitumor activity in murine models glioblastoma. Galunisertib (300 mg/day) given orally 14 days on/14 off (intermittent dosing). Lomustine as approved. Patients were randomized 2:1:1 ratio galunisertib + lomustine, monotherapy, or placebo lomustine. primary objective overall survival (OS); secondary objectives safety, pharmacokinetics (PKs), activity. One...
Galunisertib is the first-in-class, first-in-human, oral small-molecule type I transforming growth factor-beta receptor (ALK5) serine/threonine kinase inhibitor to enter clinical development. The effect of galunisertib vs. placebo in patients with unresectable pancreatic cancer was determined.This a two-part, multinational study: phase 1b non-randomised, open-label, multicentre, and dose-escalation study; 2 randomised, placebo- Bayesian-augmented controlled, double-blind study locally...
TGFβ signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block and reduce progression preclinical models. To use the treatment of malignancies, we investigated its properties first-in-human dose (FHD) study patients with cancer.Sixty-five (58 glioma) measurable progressive malignancies were enrolled. Oral was given split morning evening on an intermittent schedule 14 days off (28-day cycle)....
INTRODUCTION: Inhibition of tumor growth factor-β (TGF-β) receptor type I potentiated the activity sorafenib in preclinical models hepatocellular carcinoma (HCC). Galunisertib is a small-molecule selective inhibitor TGF-β1 I, which demonstrated phase 2 trial as second-line HCC treatment. METHODS: The combination galunisertib and (400 mg BID) was tested patients with advanced Child-Pugh A liver function without prior systemic therapy. dose administered 80 or 150 b.i.d. orally for 14 days...
Background We assessed the safety, efficacy, and pharmacokinetics of transforming growth factor beta (TGFβ) receptor inhibitor galunisertib co-administered with anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated ≤2 systemic regimens. Methods This was a two-part, single-arm, multinational, phase Ib study. In dose-finding phase, escalating oral doses were on days 1–14 fixed-dose intravenous 1500 mg day every 4...
Importance β-amyloid plaques and neurofibrillary tau deposits biologically define Alzheimer disease. Objective To perform post hoc analyses of amyloid reduction after donanemab treatment assess its association with pathology clinical measures. Design, Setting, Participants The Study LY3002813 in With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ) was a phase 2, placebo-controlled, randomized trial conducted from December 18, 2017, to 4, 2020, double-blind period up 76 weeks 48-week...
Donanemab is an amyloid-targeting therapy that resulted in robust amyloid plaque reduction and slowed Alzheimer's disease (AD) progression compared with placebo the phase II TRAILBLAZER-ALZ study (NCT03367403). The objectives of current analyses are to characterize (i) population pharmacokinetics donanemab, (ii) relationship between donanemab exposure (response), (iii) amyloid-related imaging abnormalities edema or effusions (ARIA-E). Model development included data from participants mild...
We assessed the activity of galunisertib, a small molecule inhibitor transforming growth factor beta (TGF-β1) receptor I, in second-line patients with hepatocellular carcinoma (HCC) two cohorts baseline serum alpha fetoprotein (AFP).Patients advanced HCC who progressed on or were ineligible to receive sorafenib, Child-Pugh A/B7 and ECOG PS ≤1 enrolled into Part A (AFP ≥ 1.5× ULN) B < ULN). Patients treated 80 150 mg galunisertib BID for 14 days per 28-day cycle. Endpoints time-to-progression...
Summary Purpose Transforming growth factor-beta (TGF-β) signaling plays a key role in epithelial-mesenchymal transition (EMT) of tumors, including malignant glioma. Small molecule inhibitors (SMI) blocking TGF-β reverse EMT and arrest tumor progression. Several SMIs were developed, but currently only LY2157299 monohydrate (galunisertib) was advanced to clinical investigation. Design The first-in-human dose study had three parts (Part A, escalation, n = 39; Part B, safety combination with...
Summary Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib temozolomide-based radiochemotherapy (TMZ/RTX) newly diagnosed glioma (NCT01220271). Methods is an open-label, 2-arm study ( N = 56) (intermittent dosing: 14 days on/14 off per cycle 28 days) combination TMZ/RTX n 40), versus control arm (TMZ/RTX,...
PURPOSE SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy metastatic pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS SEQUOIA, randomized, global phase III study, FOLFOX PEG + as second line gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG FOLFOX:FOLFOX)...
Abstract Background In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib nivolumab. Methods Eligible were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, treatment-naive for anti-programmed death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib open-label, dose-escalation...
Transforming growth factor-beta (TGF-β) signaling plays an important role in the fetal development of cardiovascular organs and repair mechanisms heart. Hence, inhibitors TGF-β pathway require a careful identification safe therapeutic window comprehensive monitoring system. Seventy-nine cancer patients (67 glioma 12 solid tumor) enrolled first-in-human dose study received inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (n = 53) or combination with lomustine 26). All were monitored...
To identify prospectively a safe therapeutic window for administration of novel oral transforming growth factor β (TGF-β) inhibitor, LY2157299 monohydrate, based on pharmacokinetic/pharmacodynamic (PK/PD) model. Simulations population plasma exposures and biomarker responses in tumour were performed future trials glioblastoma other cancer populations.The model was updated after completion each cohort during the first-in-human dose (FHD) study. The flexible design allowed continuous...
Abstract Purpose: Overactivation of TGF-β signaling is observed in myelodysplastic syndromes (MDS) and associated with dysplastic hematopoietic differentiation. Galunisertib, a first-in-class oral inhibitor the receptor type 1 kinase (ALK5) has shown effectiveness preclinical models MDS acceptable toxicity phase I studies solid malignancies. Patients Methods: A II multicenter study galunisertib was conducted patients very low-, or intermediate-risk by Revised International Prognostic Scoring...
Preclinical data suggest that vascular endothelial growth factor (VEGF) and transforming (TGF)-β signaling interact to stimulate angiogenesis suppress antitumor immune responses. Thus, combined inhibition of both pathways may offer greater activity compared with VEGF-targeted antiangiogenic monotherapy against hepatocellular carcinoma (HCC).This is a multicenter, open-label, phase 1b study galunisertib, an inhibitor TGF-β receptor 1, ramucirumab, anti-VEGF 2 antibody, in patients advanced...
Abstract INTRODUCTION TRAILBLAZER‐ALZ 6 (NCT05738486) is a multicenter, double‐blind, ongoing phase 3b study in early symptomatic Alzheimer's disease. METHODS Participants ( n = 843) were randomized 1:1:1:1 (standard + three alternative donanemab dosing arms). Primary outcome was relative risk reduction (RRR) of amyloid‐related imaging abnormalities with edema/effusions (ARIA‐E) at 24 weeks assessed Bayesian logistic regression. Amyloid plaque levels by positron emission tomography and serum...