A5084431593- Fibroblast Growth Factor Research
- Cell death mechanisms and regulation
- Cancer Treatment and Pharmacology
- Medical Imaging and Pathology Studies
- Sarcoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Multiple Myeloma Research and Treatments
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related Molecular Pathways
- Chemotherapy-related skin toxicity
- Head and Neck Cancer Studies
- PARP inhibition in cancer therapy
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Eosinophilic Disorders and Syndromes
- Kruppel-like factors research
- Metastasis and carcinoma case studies
- Ubiquitin and proteasome pathways
- Medical Imaging Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Hormonal Regulation and Hypertension
- Retinoids in leukemia and cellular processes
- Advanced Radiotherapy Techniques
Debiopharm (Switzerland)
2014-2024
Sigma Tau (Italy)
2000-2011
Bristol-Myers Squibb (France)
2011
Centre Léon Bérard
2007
Hôpital Edouard Herriot
2007
Université Claude Bernard Lyon 1
2007
Fondazione IRCCS Istituto Nazionale dei Tumori
2007
Sigma-Tau (Switzerland)
2000-2004
Azienda Ospedaliera S.Maria
2004
Janssen (Italy)
1990-1993
Abstract Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a major side effect of several antineoplastic drugs. However, despite its clinical importance, there no agreement as to the best way assess severity and changes in CIPN. We have previously demonstrated correlation between CIPN, assessed using Total Neuropathy Score (TNS) or reduced versions, common toxicity scales. In this study, we investigated two series patients (total number = 173) who were evaluated at baseline during...
To investigate tolerability, efficacy, and pharmacokinetics/pharmacodynamics of Debio 1347, a selective FGFR inhibitor.This was first-in-human, multicenter, open-label study in patients with advanced solid tumors harboring FGFR1-3 gene alterations. Eligible received oral 1347 at escalating doses once daily until disease progression or intolerable toxicity. Dose-limiting toxicities (DLT) were evaluated during the first 4 weeks on treatment, postfirst dose after weeks.A total 71 screened 58...
We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within tree. In addition to frequent FGFR2 fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) IHCC, including two p.H167_N173del. Expression this EID NIH3T3 cells resulted constitutive activation, oncogenic transformation, sensitivity FGFR inhibitors. Three EIDs were...
The authors compared clinically based neurotoxicity scales with the Total Neuropathy Scale, aim of improving grading severity chemotherapy-induced peripheral neuropathy (CIPN). CIPN was evaluated in a series 60 women treated cisplatin- and paclitaxel-based chemotherapy. A reduced version TNS (TNSr) also compared. concluded that TNSr can be used to assess effectively, results this evaluation reliably correlated oncologic sensory neurotoxicity.
To assess safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of DEBIO1143, an antagonist inhibitor apoptosis proteins.This first-in-man study in patients with advanced cancer used accelerated dose titration design. DEBIO1143 was given orally once daily on days 1-5 every 2 or 3 weeks until disease progressed dropped out. The starting 5 mg escalated by 100% single related grade toxicity occurred. This triggered expansion to cohorts three subsequently six...
Aims and background In addition to bone marrow suppression renal toxicity, neurotoxicity is a commonly occurring side effect of widely used chemotherapeutic agents like taxanes, cisplatin vinca alkaloids. Neurotoxicity can cause antitumor therapy discontinuation or dose regimen modification. The aim the present exploratory study was investigate activity acetyl-L-carnitine in reversing peripheral neuropathy patients with chemotherapy-induced neuropathy. Methods design Twenty-seven (16 males...
The assessment of chemotherapy‐induced peripheral neurotoxicity (CIPN) is still uncertain as several the most frequently used scales do not rely on a formal neurological evaluation and depend patients' reports examiners' interpretations. aim this study was to compare CIPN using National Cancer Institute Common Toxicity Criteria (NCI‐CTC) scale scored with Total Neuropathy Score (TNS, i.e., composite designed grade impairment in neuropathy patients) identify possible discrepancies diagnosis....
Xevinapant is a first-in-class antagonist of inhibitor apoptosis proteins, which enhances cancer cell sensitivity to chemotherapy and radiotherapy. In phase II randomized study in patients with unresected locally advanced squamous carcinoma the head neck (LA SCCHN), xevinapant plus standard-of-care cisplatin-based chemoradiotherapy (CRT) showed superior efficacy versus placebo CRT. Here, we describe design TrilynX (NCT04459715), randomized, double-blind, III study. total, 700 LA SCCHN will...
3603 Background: Debio 1347 is a selective oral inhibitor of FGFR 1-3 tyrosine kinases. It exhibited high antitumor activity in vitro and vivo tumor models with FGFR1-3 gene fusions. Here we report the results expansion portion Phase 1 study advanced solid tumors patients (pts) harboring an fusion. Methods: Pts refractory fusion were enrolled. Based on from dose escalation portion, pts received Debio1347 80 mg once daily (qd) 28-day cycles. Pharmacokinetics (PK) pharmacodynamics evaluated....
Abstract Purpose: Debio 1143 is an oral antagonist of inhibitor apoptosis proteins, which enhances tumor response with concomitant chemoradiotherapy. Addition to cisplatin-based chemoradiotherapy in locally advanced squamous cell carcinomas the head and neck (LA-SCCHN) was evaluated a phase I/II study determine MTD recommended II dose (RP2D). Here, I results are reported. Patients Methods: Treatment-naïve patients LA-SCCHN (stages III/IVA/IVB) received (100, 200, 300 mg/day), for 14 days...
TPS3157 Background: Dysregulation of fibroblast growth factor receptor (FGFR) signaling by FGFR fusions is implicated in many cancers. Debio 1347 a selective oral inhibitor 1-3 tyrosine kinases. It exhibited high antitumor activity vitro and vivo tumor models with FGFR1-3 gene fusions. Preliminary data from an ongoing phase 1 trial show efficacy tolerability patients (pts) harboring fusion irrespectively type. We present the design for multicenter, basket, 2-stage, adaptive single arm Phase...
Abstract Inhibitor of apoptosis proteins (IAPs) regulate and modulate NF‐κB signaling thereby driving expression genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response chemoradiotherapy and/or immunotherapy. Patients with pre‐operative squamous cell carcinomas the head neck (SCCHN) received: monotherapy (200 mg/day [D]1–15 +/‐ 2); D1–15 2) plus cisplatin (40 mg/m 2 D 1 8); alone 8; EudraCT: 2014‐004655‐31)....
This multicenter phase II basket trial investigated the efficacy, safety, and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor FGFR1-3, in patients with solid tumors harboring a functional FGFR1-3 fusion.
Background: Cholangiocarcinoma (CCA), an aggressive epithelial neoplasm of biliary tract, presents limited treatment options and poor overall survival. Aberrant fibroblast growth factor receptor (FGFR) signaling has been implicated in CCA carcinogenesis especially intrahepatic cholangiocarcinoma (iCCA). Debio 1347 is orally available selective FGFRi with potent antitumor effect preclinical models cancer bearing FGFR alterations. showed encouraging preliminary clinical activity manageable...
Abstract Purpose: In a continuous effort to seek for anticancer treatments with minimal side effects, we aim at proving the feasibility of Intraoperative Avidination Radionuclide Therapy, new procedure partial breast irradiation. Experimental Design: To assess doses 90Y-DOTA-biotin target (i.e., tumor bed) and nontarget organs, did simulation studies 111In-DOTA-biotin in 10 candidates conservative surgery. Immediately after quadrantectomy, patients were injected 100-mg avidin bed. On...
2500 Background: Oncogenic alterations in fibroblast growth factor receptors (FGFR) are seen across multiple solid tumor malignancies. Debio 1347 is an orally available, highly selective panFGFR inhibitor with potent antitumor effect preclinical models bearing FGFR1-3 genetic alterations. Methods: Patients harboring defined FGFR 1, 2 or 3 received escalating doses of starting from 10 mg once daily. Dose escalation followed a 3+3+3 algorithm based on modified Fibonacci sequence. The MTD was...