A5014360658- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Adenosine and Purinergic Signaling
- Pharmacogenetics and Drug Metabolism
- Immune Cell Function and Interaction
- Brain Metastases and Treatment
- Immunotherapy and Immune Responses
- Drug Transport and Resistance Mechanisms
- CAR-T cell therapy research
- Cancer Research and Treatments
- Bacteriophages and microbial interactions
- Antibiotics Pharmacokinetics and Efficacy
- Cell Adhesion Molecules Research
- Plant Virus Research Studies
- Polyomavirus and related diseases
- Click Chemistry and Applications
Ono Pharmaceutical (United States)
2022-2025
Background M6223 is an intravenous (IV), Fc-competent, fully human, antagonistic, anti-T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) antibody. Bintrafusp alfa (BA) a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β PD-(L)1 pathways. Methods This first-in-human, dose-escalation study in patients advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated alone (Part 1A, n=40; 10–2400 mg every 2...
Refining dose projections requires a deep understanding of drug-target relationships at the site action, which is often challenging to achieve. Here we present case study how one can refine for TIGIT-targeted immunotherapy by leveraging information from well-studied PD-1 pathway since co-expression and TIGIT on immune cells provides unique opportunity extrapolate data target inform dosing strategy other. We develop fit-for-purpose mathematical model that captures experimentally observed...
Abstract Like other monoclonal antibodies, immune checkpoint inhibitors may be immunogenic in some patients, potentially affecting pharmacokinetics (PKs) and clinical outcomes. In post hoc analyses, we characterized antidrug antibody (ADA) development with avelumab monotherapy patients metastatic Merkel cell carcinoma (mMCC) from the JAVELIN 200 trial (first‐line [1L; N = 116] second‐line or later [≥2L; 88] cohorts) advanced urothelial (aUC) Bladder 100 (1L maintenance [ 350]) Solid Tumor...
Abstract Introduction: M6223 is an intravenous (IV), fully human, antagonistic, anti-TIGIT antibody with Fc-mediated effector region. In preclinical studies, combined BA (a bifunctional fusion protein that simultaneously targets the TGF-β and PD-(L)1 pathways) enhanced antitumor efficacy compared to either agent alone. Methods: This first-in-human, dose escalation study of as monotherapy (M6223; Part 1A) or in combination (M6223+BA; 1B) included pts advanced solid tumors (aged ≥18 years,...
Abstract A2A and A2B adenosine receptors have been shown to mediate immunosuppressive tumor-promoting signals in the tumor microenvironment their inhibition may be a promising treatment strategy for patients with advanced solid tumors. Dual A2A/A2B has an acceptable safety profile as monotherapy early signs of clinical activity combination chemotherapy M1069 is novel, orally administered, highly selective dual antagonist that recently demonstrated significant anti-tumor vivo chemotherapeutic...