A5102963662- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Ocular Oncology and Treatments
- Advanced Breast Cancer Therapies
- Immune Cell Function and Interaction
- Melanoma and MAPK Pathways
- Lymphoma Diagnosis and Treatment
- Cutaneous Melanoma Detection and Management
- Lung Cancer Research Studies
- Occupational and environmental lung diseases
- Toxin Mechanisms and Immunotoxins
- Synthesis and Biological Evaluation
- Neuroblastoma Research and Treatments
- Peptidase Inhibition and Analysis
- Nonmelanoma Skin Cancer Studies
- Whipple's Disease and Interleukins
- Chromatin Remodeling and Cancer
- Pancreatic and Hepatic Oncology Research
- Adenosine and Purinergic Signaling
Novartis (United States)
2020-2023
Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for treatment patients with advanced/metastatic solid tumors ±the anti-programmed cell death-1 antibody, spartalizumab.
3012 Background: LAG525 and spartalizumab (PDR001), humanized IgG4 mAbs, block binding of LAG-3 to MHC class II PD-1 PD-L1 PD-L2, respectively. Preclinical studies show synergistic anti-tumor activity when blocking LAG-3. Here, we report dose escalation results from a Phase I/II study ± in advanced malignancies (NCT02460224). Methods: was dosed Q2W (1–15 mg/kg, or 240/400 mg) Q4W (3–10 400 mg); + at 15 levels/schedules 0.3 mg/kg 1 1000 mg Q4W. I endpoints (dose-limiting toxicities [DLTs],...
Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed evaluate the safety and efficacy orally available protein kinase C inhibitor, AEB071, in UM, perform genomic profiling tumor samples, aim propose combination therapies. Patients UM (n = 153) were treated AEB071 a phase I, single-arm study. received total daily doses ranging from 450 1,400 mg. First-cycle dose-limiting toxicities observed 13 (13%)....
Background NIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, promotes cytotoxic lymphocyte proliferation, killing function, organ/tumor infiltration, with resultant anticancer effects. this first-in-human study, we assessed the safety, pharmacokinetics, immune effects in patients metastatic or unresectable solid tumors. Methods Single agent dose escalation data are reported from phase I escalation/expansion...
Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab phase 1 study. This 2 study aimed to further investigate efficacy and safety of treatment patients selected advanced (locally or metastatic) solid malignancies. Eligible non-small cell lung cancer (NSCLC), melanoma, renal carcinoma (RCC), mesothelioma, triple-negative breast (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive...
<h3>Background</h3> Expression of LAG-3, an inhibitory immunoreceptor, has been linked to reduced T-cell proliferation and cytokine production. LAG525 is a humanized IgG4 anti-LAG-3 antibody which inhibits LAG-3 binding MHC class II. Spartalizumab anti-PD-1 mAb PD-1 with its ligands PD-L1 PD-L2. Preclinical data have shown promising antitumor activity when blocking PD-1. <h3>Methods</h3> The Phase II part the first-in-human study (NCT02460224) explored + spartalizumab in patients...
Abstract Background: NIZ985 is a soluble IL-15/IL-15 receptor α heterodimer (hetIL-15) that binds IL-2/IL-15 β/γ and promotes effector T-cell NK cell expansion activation. Spartalizumab humanized IgG4 mAb blocks binding of programmed death 1 (PD-1) to ligand 1/2 (PD-L1/2). In preclinical studies, IL-15 anti-PD-1/PD-L1 combinations demonstrated synergistic antitumor activity. Here we report dose escalation results from Ph I/Ib study as single agent (SA) in combination with spartalizumab...
Background: NIZ985 is a soluble IL-15/IL-15 receptor α heterodimer (hetIL-15) that binds IL-2/IL-15 β/γ and promotes effector T-cell NK cell expansion activation. Spartalizumab humanized IgG4 mAb blocks binding of programmed death 1 (PD-1) to ligand 1/2 (PD-L1/2). In preclinical studies, IL-15 anti-PD-1/PD-L1 combinations demonstrated synergistic antitumor activity. Here we report dose escalation results from Ph I/Ib study as single agent (SA) in combination with spartalizumab...
<div>Abstract<p>Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed evaluate the safety and efficacy orally available protein kinase C inhibitor, AEB071, in UM, perform genomic profiling tumor samples, aim propose combination therapies. Patients UM (<i>n</i> = 153) were treated AEB071 a phase I, single-arm study. received total daily doses ranging from 450 1,400 mg. First-cycle...
<div>Abstract<p>Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed evaluate the safety and efficacy orally available protein kinase C inhibitor, AEB071, in UM, perform genomic profiling tumor samples, aim propose combination therapies. Patients UM (<i>n</i> = 153) were treated AEB071 a phase I, single-arm study. received total daily doses ranging from 450 1,400 mg. First-cycle...
<h3>Background</h3> HEK-NIZ985 (NIZ985) is a recombinant heterodimer of IL-15/IL-15Rα that expands effector lymphocytes and antitumor activity in animal models human clinical trial. We report interim data from the first-in-human study NIZ985. <h3>Methods</h3> CNIZ985X2102J an open-label Phase I/Ib dose-escalation/expansion trial evaluating safety subcutaneous NIZ985 three-times-weekly (TIW; 2-weeks-on/2-weeks-off) or once-weekly (QW; 3-weeks-on/1-week-off) as single agent (SA) combination...