A5070634479- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Sphingolipid Metabolism and Signaling
- Estrogen and related hormone effects
- Sleep and Wakefulness Research
- HER2/EGFR in Cancer Research
- Regulation of Appetite and Obesity
- Lung Cancer Treatments and Mutations
- Sleep and related disorders
- Breast Cancer Treatment Studies
- Eosinophilic Disorders and Syndromes
- Circadian rhythm and melatonin
- Radiopharmaceutical Chemistry and Applications
- Quinazolinone synthesis and applications
- Statistical Methods in Clinical Trials
- Multiple Sclerosis Research Studies
- Advanced Breast Cancer Therapies
- Acute Lymphoblastic Leukemia research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Biochemical Analysis and Sensing Techniques
- Adipokines, Inflammation, and Metabolic Diseases
- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Cytokine Signaling Pathways and Interactions
Novartis (Switzerland)
2021-2025
Institute of Hematology & Blood Diseases Hospital
2024
Cancer Research Institute
2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2024
Jena University Hospital
2024
Charité - Universitätsmedizin Berlin
2024
Novartis Institutes for BioMedical Research
2021-2024
Hudson Institute
2023
EVRAZ (United Kingdom)
2023
John Wiley & Sons (United States)
2023
Patients with newly diagnosed chronic myeloid leukemia (CML) need long-term therapy high efficacy and safety. Asciminib, a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket, may offer better safety fewer side effects than currently available frontline ATP-competitive tyrosine kinase inhibitors (TKIs).
Purpose: AZD9496 is an oral nonsteroidal, small-molecule inhibitor of estrogen receptor alpha (ERα) and a potent selective antagonist degrader ERα. This first-in-human phase I study determined the safety tolerability ascending doses in women with (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, made preliminary assessment antitumor activity.Patients Methods: Forty-five patients received [20 mg once daily (QD) to 600 twice (BID)] dose-escalation,...
Abstract Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing safety, tolerability, and antileukemic activity asciminib monotherapy 10–200 mg once twice daily in 115 CML-CP without (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6%...
Abstract Purpose: Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations the ligand-binding domain of gene (ESR1LBDm). ESR1 mutational mediated may be overcome by selective degraders (SERD). During first-in-human study oral SERD AZD9496, early changes circulating tumor cells (CTCs) DNA (ctDNA) were explored as potential noninvasive tools, alongside paired biopsies,...
The protein kinase ataxia telangiectasia mutated (ATM) mediates cellular response to DNA damage induced by radiation. ATM inhibition decreases repair in tumor cells and affects growth. AZD1390 is a novel, highly potent, selective inhibitor designed cross the blood-brain barrier (BBB) currently evaluated with radiotherapy phase I study patients brain malignancies. In present study, PET was used measure exposure of 11C-labeled after intravenous (i.v.) bolus administration healthy subjects an...
Asciminib (Scemblix) is a first‐in‐class BCR::ABL1 inhibitor that works by specifically targeting the ABL myristoyl pocket (STAMP) and has potent activity against T315I mutation. This study aimed to characterize effect of asciminib exposure on disease progression elucidate factors influencing efficacy. Our analysis included 303 patients with chronic myeloid leukemia in phase recruited I dose ranging from 10 200 mg twice day (b.i.d.) or 40 once (q.d.) (NCT02081378) III ASCEMBL (Study Efficacy...
Abstract Asciminib is the first approved BCR::ABL1 inhibitor that Specifically Targets ABL Myristoyl Pocket (STAMP). The present final analysis of phase 1, open-label, nonrandomized trial (NCT02081378) assessed long-term safety, tolerability, and antileukemic activity asciminib in 115 patients with chronic myeloid leukemia without T315I mutation who received 10–200 mg twice daily (BID) or 80–200 once (cutoff: March 14, 2023). Median exposure duration was 5.9 (range, 0–8.4) years; 60.9%...
Data from in vitro and animal studies suggest that asciminib, the first BCR::ABL1 inhibitor Specifically Targets ABL Myristoyl Pocket (STAMP), synergizes with adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) to prevent emergence of overcome resistance. Combination therapy may provide new treatment options for patients chronic myeloid leukemia (CML) suboptimal responses ATP-competitive TKI monotherapy. Preliminary analysis asciminib combined nilotinib, imatinib, or...
Abstract Objective: The melanocortin system is a key regulator in the hypothalamus of energy intake and expenditure. It frequently linked with obesity apparently modulates sympathetic outflow to white adipose tissues. role melanocortins within tissues, however, not entirely clear. This study was aimed at determining quantitative expression five receptors (MC1‐R MC5‐R) subcutaneous omental fat obese patients non‐obese subjects. Research Methods Procedures: Expression MC1‐R MC5‐R,...
6562 Background: For pediatric pts with Ph+ CML-CP, treatment options improved efficacy and long-term safety are needed. ASC is a first-in-class tyrosine kinase inhibitor (TKI) Specifically Targeting the ABL Myristoyl Pocket (STAMP), approved for adults CML-CP treated ≥2 prior TKIs. The phase Ib/II ASC4KIDS study (NCT04925479) aims to characterize pharmacokinetics (PK) profile of in pts. Methods: This multi-center, open-label included aged 1–<18 years (yrs) without T315I mutation, ≥1...
Abstract A double‐blind, placebo‐ and active comparator‐controlled, randomized, single‐ascending‐dose study was conducted to investigate the safety, pharmacokinetics, pharmacodynamics of ACT‐462206, a novel dual orexin receptor antagonist. Healthy male subjects received single oral doses 5, 25, 100, 200, 400, 1,000, 1,500 mg ACT‐462206 (n = 6 per group) or placebo 2 group). In addition, in 400‐mg group dose 400 almorexant (two‐way crossover). generally well tolerated. Sleepiness, headache,...
Abstract: The effects of selexipag and its active metabolite ACT-333679 on cardiac repolarization were assessed in a thorough QT study as per International Conference Harmonisation E14 guidance. In this randomized, double-blind, placebo/positive-controlled, parallel-group study, healthy male female subjects randomized to receive escalating doses (n=91) or placebo/moxifloxacin (n=68). Ascending multiple the range 400-1,600 µg placebo administered twice daily for 21 days. Following nested...
Abstract Asciminib is an investigational, first‐in‐class, specifically targeting the ABL myristoyl pocket (STAMP) inhibitor of BCR‐ABL1 with a new mechanism action compared approved ATP‐competitive tyrosine kinase inhibitors. This report describes findings from 2 phase 1 studies assessing pharmacokinetic (PK) profile single dose asciminib (40 mg) in individuals impaired renal function (based on absolute glomerular filtration rate; NCT03605277) or hepatic Child‐Pugh classification;...
1. Ponesimod [(R)-5-[3-chloro-4-(-2,3-dihydroxy-propoxy)-benzylidene]-2-propylimino-3-o-tolyl-thiazolidin-4-one] is an orally administered, selective S1P1 receptor modulator that blocks the egress of lymphocytes from lymphoid organs and reduces availability circulating effector T/B-cells.2. The mass balance, pharmacokinetics metabolism 40 mg 14C-ponesimod were investigated in six healthy male subjects. total radioactivity whole blood, plasma, urine, faeces expired CO2 was determined by...
Abstract Asciminib, a first‐in‐class BCR‐ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP), is new treatment option for patients with chronic myeloid leukemia who no longer benefit from currently approved tyrosine kinase inhibitors. In vitro, asciminib reversibly inhibits cytochrome P450 (CYP) 3A4/5, CYP2C9, and CYP2C8. This phase I, open‐label, two‐stage study in healthy participants evaluated effect of (40 mg b.i.d. at steady‐state) as potential...
Abstract Asciminib is a first‐in‐class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. substrate CYP3A4 and P‐glycoprotein (P‐gp) possesses pH‐dependent solubility in aqueous solution. This report summarizes results two phase I studies healthy subjects aimed at assessing impact CYP3A P‐gp inhibitors, inducers acid‐reducing agents (ARAs) on pharmacokinetics (PK) asciminib (single dose 40 mg). exposure (area under curve [AUC]) unexpectedly decreased by ~40% when...