Ruxolitinib cream monotherapy demonstrates rapid improvement in the extent and signs of mild to moderate atopic dermatitis across head and neck and other anatomic regions in adolescents and adults: pooled results from 2 phase 3 studies.

Ruxolitinib (selective Janus kinase [JAK] 1 and JAK2 inhibitor) cream demonstrated efficacy and safety in patients with atopic dermatitis (AD) in the phase 3 TRuE-AD studies. In TRuE-AD1/TRuE-AD2 (NCT03745638/NCT03745651), adults and adolescents with mild to moderate AD were randomized to apply twice-daily ruxolitinib cream or vehicle for eight weeks. Here, we evaluated the efficacy and tolerability of ruxolitinib cream by anatomic region, focusing on head/neck (HN) lesions that are typically difficult to manage and disproportionately affect quality of life (QoL).

Clinically relevant improvements in adults and adolescents with atopic dermatitis who did not achieve Investigator's Global Assessment treatment success following 8 weeks of ruxolitinib cream monotherapy.

Ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and JAK2. In two phase 3 studies in adults and adolescents (aged ≥12 years) with atopic dermatitis (AD; TRuE-AD1/TRuE-AD2), significantly more patients who applied ruxolitinib cream versus vehicle cream achieved Investigator's Global Assessment treatment success (IGA-TS; IGA score of 0/1 with ≥2-point improvement from baseline) at week 8 (primary endpoint). This post hoc analysis evaluated the efficacy, safety, and disease control of ruxolitinib cream in patients with AD who did not achieve IGA-TS at week 8.

Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies.

Background: Ruxolitinib cream demonstrated safety and efficacy over 8 weeks in 2 double-blind phase 3 atopic dermatitis studies (NCT03745638/NCT03745651).

Objective: To evaluate long-term safety (LTS) and disease control with ruxolitinib cream.

Methods: Patients initially randomized to twice-daily 0.

Correction: Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer.

[This corrects the article DOI: 10.1371/journal.pone.

Correction: Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer.

[This corrects the article DOI: 10.1371/journal.pone.

A First-in-Human Dose Finding Study of Camrelizumab in Patients with Advanced or Metastatic Cancer in Australia.

Purpose: Camrelizumab inhibits PD-1 in non-clinical models and showed typical non-clinical pharmacokinetic (PK) and safety profiles for an IgG4 monoclonal antibody. We report results from the First-in-Human Phase 1 trial of camrelizumab in Australian population.

Methods: Camrelizumab was administered to patients with advanced solid tumors who had failed standard therapies.

A Phase I/II Multicenter Study of Single-Agent Foretinib as First-Line Therapy in Patients with Advanced Hepatocellular Carcinoma.

This phase I/II single-arm study evaluated the safety, pharmacokinetics, pharmacodynamics, and activity of foretinib, an oral multikinase inhibitor of MET, ROS, RON, AXL, TIE-2, and VEGFR2, in the first-line setting in advanced hepatocellular carcinoma patients. In the phase I part, advanced hepatocellular carcinoma patients were dose escalated on foretinib (30-60 mg) every day using the standard 3+3 design. Once the maximum tolerated dose (MTD) was determined, an additional 32 patients were dosed at the MTD in the phase II expansion cohort for assessment of efficacy and safety.

Population pharmacokinetics modeling and analysis of foretinib in adult patients with advanced solid tumors.

Foretinib is a multikinase inhibitor that inhibits multiple receptor tyrosine kinases, including MET and VEGFR, with the potential for treatment of solid tumors. Hepatocellular carcinoma (HCC) pathogenesis is associated with overexpression of MET, and physiologic changes in the livers of HCC patients may decrease CYP3A isozyme-mediated metabolism of foretinib. A population pharmacokinetic model of foretinib was developed to explore the effect of tumor type, formulation, and other covariates.

Phase II study evaluating 2 dosing schedules of oral foretinib (GSK1363089), cMET/VEGFR2 inhibitor, in patients with metastatic gastric cancer.

Purpose: The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma.

Patients And Methods: Foretinib safety and tolerability, and objective response rate (ORR) were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks) or daily (80 mg/day) dosing schedules.

Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Background: Foretinib is a small-molecule, oral multikinase inhibitor primarily targeting the mesenchymal epithelial transition (MET) factor receptor, and the vascular endothelial growth factor receptor 2. We conducted a phase II study to evaluate the single-agent activity and tolerability of foretinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).

Methods: An open-label, single-arm, multicenter trial employing a Simon 2-stage design was conducted with a total of 41 patients planned for the study.

Development of a scintillation proximity assay for the Mycobacterium tuberculosis KasA and KasB enzymes involved in mycolic acid biosynthesis.

Tuberculosis remains a global health problem, and programs dedicated to discovery of novel compounds against Mycobacterium tuberculosis require robust assays for high-throughput screening of chemical and natural product libraries. Enzymes involved in the biosynthesis of mycolic acids, vital components of the mycobacterial cell wall, have received much attention as potential drug targets. KasA and KasB, examples of the beta-ketoacyl-acyl carrier protein synthase I/II (KASI/II) class of condensing enzymes of the M.

Staphylococcus aureus 3-hydroxy-3-methylglutaryl-CoA synthase: crystal structure and mechanism.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, a member of the family of acyl-condensing enzymes, catalyzes the first committed step in the mevalonate pathway and is a potential target for novel antibiotics and cholesterol-lowering agents. The Staphylococcus aureus mvaS gene product (43.2 kDa) was overexpressed in Escherichia coli, purified to homogeneity, and shown biochemically to be an HMG-CoA synthase.