A5059656244- Gastric Cancer Management and Outcomes
- Colorectal Cancer Treatments and Studies
- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Breast Cancer Treatment Studies
- Bladder and Urothelial Cancer Treatments
- Drug Transport and Resistance Mechanisms
- Glaucoma and retinal disorders
- Gastrointestinal Tumor Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Cell Adhesion Molecules Research
- Esophageal Cancer Research and Treatment
- Pharmacogenetics and Drug Metabolism
- Biochemical and Molecular Research
- Cancer Treatment and Pharmacology
- Antibiotics Pharmacokinetics and Efficacy
- Ocular Surface and Contact Lens
- Inflammatory mediators and NSAID effects
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Cell Image Analysis Techniques
- Eicosanoids and Hypertension Pharmacology
- Ocular Oncology and Treatments
Daiichi Sankyo (United States)
2021-2025
Daiichi Sankyo (Germany)
2023
Daiichi-Sankyo (South Korea)
2023
Daiichi-Sankyo (Japan)
2020-2021
Ono Pharmaceutical (Japan)
2015-2017
Ibero American University
2015
Ono Pharmaceutical (United States)
2013-2014
Ono Pharmaceutical (United Kingdom)
2009
Tokyo University of Pharmacy and Life Sciences
2005
Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2
Abstract Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method quantitative continuous (QCS) digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast tissue. Candidate signatures patient stratification using QCS HER2 subcellular...
Abstract Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3 /HER3 levels. This research investigates the genetic factors affecting HER3-DXd’s response women early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) cancer. In SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered 98 patients across two parts: 78 received 6.4 mg/kg (Part A), 44 lower 5.6 B). The CelTIL score,...
Abstract Purpose: This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and urothelial (mUC). Patients Methods: Part 1 determined the recommended dose for expansion of T-DXd nivolumab. 2 evaluated efficacy safety; primary endpoint was confirmed objective response rate by independent central review. Results: In part 1, seven mBC were enrolled received 3.2 mg/kg (four patients) or 5.4 (three...
The purpose of this study was to determine whether a better IOP reduction can be observed in conscious, normotensive monkeys treated with ONO-9054, novel dual EP3 and FP receptor agonist, compared prostaglandin F2α analogs.The binding affinities agonistic activities ONO-AG-367, carboxylic acid prostanoid receptors were assessed. IOP-lowering effect ONO-9054 analyzed after single (0.3, 3, or 30 μg/mL) 7-day repeated (30 μg/mL, every day) topical ocular administration. Ophthalmologic...
<p>Immune infiltration in tumors at baseline and association with response to T-DXd therapy. <b>A,</b> Tumoral CD8<sup>+</sup> cell densities, as determined using mIHC, responders nonresponders. <b>B, </b><i>CD8A</i> <i>CD8B</i> mRNA expression levels, RNA-seq, CPM, counts per million. <b>C,</b> Relationship between immune densities for cells expressing CD4, CD68, CD20, CD163, CD208, CD1a, mIHC IHC....
<p>Unsupervised hierarchical clustering analysis based on cell densities of evaluated immune cells at baseline. <b>A,</b> Heatmap depicting unsupervised results and characteristics the three observed groups. <b>B, </b><i>ERBB2</i> expression levels in groups obtained from clustering. <b>C,</b> Kaplan–Meier OS PFS curves 1, 2, 3 grouped by cells. CPM, counts per million; ECOG PS, Eastern Cooperative Oncology Group performance status; I/O,...
<p>Tumor-infiltrating immune cell densities at baseline and in response to T-DXd therapy responders nonresponders. <b>A,</b> Tumor-infiltrating CD8<sup>+</sup> T-cell densities, as determined using mIHC. <b>B,</b> Tumoral <i>CD8A</i> <i>CD8B</i> expression, RNA-seq. <b>C,</b> Percentage of cells CD3<sup>+</sup> baseline, FCM. <b>D,</b> Densities eTregs (Fr2)...
<p>Supplementary Figures and Tables.</p>
<div>Abstract<p>Trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody–drug conjugate with a topoisomerase I inhibitor connected by cleavable linker, has been approved for patients HER2-positive gastric or gastroesophageal junction tumors. This biomarker study assessed HER2 expression and immune cell infiltration in relation to the therapeutic response T-DXd. retrospective analysis included samples from treated T-DXd three clinical trials. We performed RNA sequencing multiplex IHC...
<p>Associations between pretreatment HER2 expression levels and therapy response to T-DXd. <b>A, </b><i>ERBB2</i> mRNA levels, as determined using RNA-seq. <b>B,</b> H-score, IHC. CPM, counts per million; CR, complete response; PD, progressive disease; PR, partial SD, stable disease.</p>
Abstract Introduction: Trastuzumab deruxtecan (T-DXd) is an innovative HER2-targeting antibody-drug conjugate comprising a HER2-specific antibody linked to exatecan derivative (DXd) payload. This therapeutic agent has demonstrated substantial clinical efficacy across various HER2-expressing malignancies. The DXd payload functions as topoisomerase I inhibitor, stabilizing the topoisomerase-DNA cleavage complex. stabilization inhibits re-ligation of DNA, leading accumulation DNA double-strand...
<p>Supplementary Figures and Tables.</p>
1020 Background: DESTINY-Breast04 (NCT03734029) showed improved progression-free survival (PFS) and overall for T-DXd vs TPC in pts with HER2-low (IHC 1+ or 2+/ISH-negative) mBC. We present exploratory biomarker analysis HER2-low, HR+ Methods: Biopsy specimens collected from 326 after prior treatment were analyzed using RNA-sequencing intrinsic subtypes estimated by PAM50 gene expression. ESR1 PIK3CA mutations known alterations associated resistance to CDK4/6 inhibitors (CDK4/6i) assessed...
Purpose: The use of a dual prostaglandin E3 (EP3) and F (FP) receptor agonist is novel approach for the reduction intraocular pressure (IOP) in open angle glaucoma ocular hypertension and, as such, ONO-9054 may have benefits over existing therapies. objectives this phase I study were to assess safety, tolerability, systemic pharmacokinetics (PK), pharmacodynamics (PD) profiles (Sepetoprost), prodrug ONO-AG-367, healthy, normotensive adults. Methods: In randomized, double-masked,...
The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic parameters up 15 dose levels ONO-4232, a selective agonist for EP4 subtype prostaglandin E2 receptor, with dual left ventricular lusitropic venodilatory action, in healthy, adult, male female volunteers.In randomized, single-center, double-blind, placebo-controlled, single-dose, sequential-group escalation, first human study, ONO-4232 (0.001, 0.003, 0.01, 0.02, 0.04, 0.08, 0.12, 0.15, 0.18, or 0.27 ng/kg/min)...
1036 Background: Trastuzumab deruxtecan (T-DXd; DS-8201) is an antibody-drug conjugate composed of anti-HER2 antibody, a cleavable linker, and cytotoxic topoisomerase I inhibitor. In the pivotal DESTINY-Breast01 trial, efficacy T-DXd in HER2-positive metastatic breast cancer (mBC) was demonstrated, with objective response rate (ORR) 60.9% median progression-free survival (mPFS) 16.4 months. Methods: single-group, open-label, multicenter, phase II trial 184 patients mBC previously treated...
To investigate safety, tolerability, and pharmacokinetic properties of single multiple doses novel translocator protein 18 kDa antagonist ONO-2952 in healthy subjects.Double-blind, placebo-controlled (SAD) (MAD) dose escalation studies were conducted. Healthy men women aged to 55 years inclusive without history psychiatric disorders eligible. Forty-eight volunteers received (3, 10, 30, 100, 200, or 400 mg) placebo under fasted conditions (SAD study), 36 (30, 60, 100 mg/d) for 21 consecutive...