Publications by authors named "P Yerramilli-Rao"
Background: Uveal melanoma is a disease characterized by constitutive activation of the G alpha pathway and downstream signaling of protein kinase C (PKC) and the mitogen-activated protein kinase (MAPK) pathway. While limited clinical activity has been observed in patients with metastatic disease with inhibition of PKC or MEK alone, preclinical data has demonstrated synergistic antitumor effects with concurrent inhibition of PKC and MEK.
Method: We conducted a phase Ib study of the PKC inhibitor sotrastaurin in combination with the MEK inhibitor binimetinib in patients with metastatic uveal melanoma using a Bayesian logistic regression model guided by the escalation with overdose control principle (NCT01801358).
Background: Up to 50% of patients with uveal melanoma develop metastases (MUM) with a poor prognosis and median overall survival of approximately 1 year.
Methods: This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the oral protein kinase C inhibitor LXS196 in 68 patients with MUM (NCT02601378). Patients received LXS196 doses ranging from 100-1000 mg once daily (QD; n = 38) and 200-400 mg twice daily (BID; n = 30).
Article Synopsis
- LAG-3 is an inhibitory receptor that regulates T-cell activation, and this study focuses on a LAG-3 inhibitor, ieramilimab (LAG525), combined with another antibody, spartalizumab, for treating patients with advanced solid tumors.
- A total of 255 patients participated in the study, receiving either single-agent ieramilimab or the combination treatment, with the primary goal of establishing the maximum tolerated dose (MTD) or recommended dose for future trials.
- The recommended doses were found to be 400 mg ieramilimab with 300 mg spartalizumab on a 3-week schedule and 800 mg and 400 mg respectively on a 4-week schedule; adverse events
Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed to evaluate the safety and efficacy of the orally available protein kinase C inhibitor, AEB071, in patients with metastatic UM, and to perform genomic profiling of metastatic tumor samples, with the aim to propose combination therapies. Patients with metastatic UM ( = 153) were treated with AEB071 in a phase I, single-arm study.
View Article and Find Full Text PDFObjective: To determine the relationships between hopelessness, depression, quality of life, and disease progression in ALS.
Methods: Hopelessness and depression were assessed prospectively in a cohort of people with ALS using the Beck Hopelessness scale (BHS) and the ALS Depression Inventory (ADI-12), respectively. ALS Specific Quality of Life and measures of functional status (ALSFRS-R and forced vital capacity) were collected.