A5009129570- Glioma Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Optimal Experimental Design Methods
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Statistical Methods in Clinical Trials
- T-cell and Retrovirus Studies
- Lung Cancer Treatments and Mutations
- Renal cell carcinoma treatment
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Bladder and Urothelial Cancer Treatments
- Vector-Borne Animal Diseases
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related Molecular Pathways
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Integrated Circuits and Semiconductor Failure Analysis
- Acute Myeloid Leukemia Research
- Pain Management and Opioid Use
- Viral Infectious Diseases and Gene Expression in Insects
- Chronic Lymphocytic Leukemia Research
- Axon Guidance and Neuronal Signaling
- Gene expression and cancer classification
- Health Systems, Economic Evaluations, Quality of Life
Daiichi-Sankyo (Japan)
2017-2025
Daiichi Sankyo (Germany)
2017-2024
Tokyo University of Science
2014-2020
Kyoto University
2019
Daiichi Sankyo (United Kingdom)
2019
Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients relapsed, recurrent, or refractory disease. We evaluated the efficacy safety of valemetostat, a potent enhancer zeste homolog 2 (EZH2) EZH1 inhibitor, in treating relapsed (R/R) ATL. This multicenter phase trial enrolled R/R ATL (acute, lymphoma, unfavorable chronic type). Patients received valemetostat 200 mg/day orally until progressive disease unacceptable...
Abstract Background Approximately 70% of lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in the accumulation oncometabolite D-2-hydroxyglutarate (D-2-HG); this leads to epigenetic dysregulation, oncogenesis, and subsequent clonal expansion. DS-1001 is an oral brain-penetrant mutant IDH1 selective inhibitor. This first-in-human study investigated safety, pharmacokinetics, pharmacodynamics, efficacy DS-1001. Methods was a multicenter, open-label,...
Abstract Milademetan (DS‐3032, RAIN‐32) is an orally available mouse double minute 2 (MDM2) antagonist with potential antineoplastic activity owing to increase in p53 through interruption of the MDM2‐p53 interaction. This phase I, dose‐escalating study assessed safety, tolerability, efficacy, and pharmacokinetics milademetan 18 Japanese patients solid tumors who relapsed after or were refractory standard therapy. Patients aged ≥ 20 years received oral once daily (60 mg, n = 3; 90 11; 120 4)...
603 Background: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to highly potent topoisomerase I inhibitor payload via plasma-stable, tumor-selective, tetrapeptide-based cleavable linker. Dato-DXd has shown encouraging antitumor activity and manageable safety profile in patients (pts) with solid tumors. We report preliminary results pts advanced/metastatic (a/m) urothelial cancer from the ongoing...
663 Background: Dato-DXd is a TROP2-directed antibody-drug conjugate under investigation in various solid tumor types. We report updated results patients (pts) with locally advanced/metastatic urothelial cancer (la/m UC) from the ongoing phase 1 TROPION-PanTumor01 study (NCT03401385). Methods: Pts unresectable la/m UC (stage III/IV) treated ≥1 prior line of therapy, including an immune checkpoint inhibitor, received 6 mg/kg Q3W. Primary objectives were safety and tolerability. Secondary...
<h3>Background</h3> Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface in many cancers and predicts poor prognosis. DS-8895a a humanized anti-EPHA2 IgG1 monoclonal antibody afucosylated to enhance antibody-dependent cellular cytotoxicity activity. We conducted two-step, phase I, multicenter, open-label study determine safety, tolerability, pharmacokinetics of patients with advanced solid tumors. <h3>Methods</h3> Step 1 was dose escalation cohort...
2004 Background: WHO grade II/III gliomas frequently harbor isocitrate dehydrogenase 1 ( IDH1) mutations, resulting in intratumoral accumulation of oncometabolite 2-hydroxyglutarate (2-HG) and subsequent clonal expansion. DS-1001b is an oral selective inhibitor mutant IDH1 R132X that was designed to penetrate the blood-brain barrier. Methods: In this first-in-human, multicenter, phase I study (NCT03030066), eligible patients (pts) with recurrent/progressive glioma received twice daily (bid),...
Abstract Background Axicabtagene ciloleucel (axi-cel) is an autologous chimeric antigen receptor T-cell based anti-CD19 therapy. The ZUMA-1 study, multicenter, single-arm, registrational Phase 1/2 study of axi-cel demonstrated high objective response rate in patients with relapsed/refractory large B-cell lymphoma. Here, we present the results bridging to evaluate efficacy and safety Japanese (JapicCTI-183914). Methods This was phase 2, open-label, single-arm trial. Following leukapheresis,...
Long-term survival in patients with acute myeloid leukemia (AML) remains low, and current treatment modalities are inadequate. Milademetan (DS-3032, RAIN-32), a small-molecule specific murine double minute 2 inhibitor, has shown p53 status-dependent antitumor effect vitro studies. This is the first phase I study report of milademetan monotherapy relapsed/refractory (R/R) AML evaluating safety, tolerability, pharmacokinetics, preliminary tumor response for further clinical development....
Background: In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an analgesic that routinely used instead of morphine cancer pain; however, it not yet available in Japan. The aim this study was to assess the efficacy and safety hydromorphone (DS-7113b) extended-release tablets opioid-naïve patients with pain relieved by non-opioid Subjects methods: This a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method blinding. Each...
Summary Recommended phase 2 doses for some drugs may differ according to a patient's clinical or genetic characteristics. We develop new method that determines the individualized optimal dose patterns of patient covariates and selects are associated with efficacy toxicity in early trials evaluating multiple interest. To address difficulty high dimensional estimation model parameters limited sample size, we propose use Bayesian least absolute shrinkage selection operator, which is penalized...
We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients unresectable locally advanced non-small-cell lung cancer. In this multicenter, single-arm, open-label, phase 2 trial conducted Japan (JapicCTI-090825), received thoracic radiotherapy (60 Gy, Gy per fraction, 6 weeks) four 4-week cycles chemotherapy (day 1, cisplatin 80 mg/m2; days 1 8, vinorelbine 20 mg/m2)....
99 Background: Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface of many tumors and associated with poor prognosis, suggesting EPHA2 as a target for cancer therapy. DS-8895a an afucosylated, humanized anti-EPHA2 IgG1 monoclonal antibody potent cytotoxicity. We report results from phase I clinical trial to determine safety, tolerability, pharmacokinetics (PK) in Japanese patients advanced solid (NCT02004717). Methods: Step 1 (dose escalation...
The aim of this study was to assess the long-term safety and efficacy sapropterin in a real-world setting Japanese patients with tetrahydrobiopterin (BH4)-responsive phenylketonuria.This post-marketing surveillance enrolled all Japan confirmed BH4-responsive PKU who were administrated between July 2008 October 2017. Patients observed at least every 3 months during follow up, key data collected on treatment exposure/duration, effectiveness according physician's judgement, serum phenylalanine...
Here, we developed a new dose-finding method that partitions cohort of patients based on the number dose combinations within prespecified acceptable toxicity range in two-agent combination Phase I trials. In proposed method, same are partitioned according to several combinations, although most existing methods allocate single-dose combination. We compared operating characteristics and through simulation studies.
Abstract BACKGROUND WHO grade II/III gliomas frequently harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in intratumoral accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG) and subsequent clonal expansion. DS-1001b is an oral selective inhibitor mutant IDH1 R132X that was designed to penetrate the blood-brain barrier. METHODS In this first-in-human, multicenter, phase I study (NCT03030066), eligible patients (pts) with recurrent/progressive glioma received twice daily...
S Kanekoa** , A Hirakawab*, Y Kakuraicd & C Hamadad†a Japan Development, Biostatistics Pharma, Integrated Japan, Novartis Pharma K.K., Minato-ku, Tokyo, Japanb Department of and Bioinformatics, Graduate School Medicine, the University Bunkyo-ku, Japanc R&D Division, Data Management, Daiichi-Sankyo Co., Ltd., Shinagawa-ku, Japand Information Computer Technology, Tokyo Science, Katsushika-ku,