Population pharmacokinetics of ipilimumab in combination with nivolumab in patients with advanced solid tumors

AbstractIpilimumab is a fully human monoclonal antibody approved for the treatment of melanoma as monotherapy and for the treatment of melanoma, renal cell carcinoma, and colorectal cancer in combination with nivolumab. Ipilimumab time ‐varying clearance (CL) was assessed by a population pharmacokinetics (PPK) model developed using statistically significant covariates identified in a previous PPK analysis plus additional covariates. Data from 3,411 patients who received ipilimumab 0.3–10 mg/kg alone or in combination with niv olumab in 16 clinical trials were analyzed. Ipilimumab CL decreased over time; the change in CL was greater in patients treated with nivolumab combination than ipilimumab alone, and in responders vs. nonresponders. Time‐varying covariates including body weight, lactate dehydrogenase, albumin, and performance status were evaluated on change in ipilimumab CL. In addition, ipilimumab CL was similar across different tumor types, nivolumab dosing regimens, and lines of therapy. These data suggest an association of ipilimumab CL with disease severity.
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research

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AbstractNivolumab is a fully human monoclonal antibody that inhibits programmed cell death ‐1 activation. To assess covariate effects on nivolumab clearance (CL), a population pharmacokinetics model was developed using data from 6,468 patients with colorectal cancer, hepatocellular carcinoma, melanoma, non‐small cell lung cancer, renal cell carcinoma, or small cell lung cancer who rec eived nivolumab as monotherapy or in combination with ipilimumab or chemotherapy across 25 clinical studies. Nivolumab CL was similar across the tumor types examined; CL was higher for ipilimumab 1 mg/kg every 6 weeks (by 17%) and 3 mg/kg...
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research
AbstractNivolumab is a fully human monoclonal antibody that inhibits programmed cell death ‐1 activation. To assess covariate effects on nivolumab clearance (CL), a population pharmacokinetics model was developed using data from 6,468 patients with colorectal cancer, hepatocellular carcinoma, melanoma, non‐small cell lung cancer, renal cell carcinoma, or small cell lung cancer who rec eived nivolumab as monotherapy or in combination with ipilimumab or chemotherapy across 25 clinical studies. Nivolumab CL was similar across the tumor types examined; CL was higher for ipilimumab 1 mg/kg every 6 weeks (by 17%) and 3 mg/kg...
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research
AbstractIpilimumab is a fully human monoclonal antibody approved for the treatment of melanoma as monotherapy and for the treatment of melanoma, renal cell carcinoma, and colorectal cancer in combination with nivolumab. Ipilimumab time ‐varying clearance (CL) was assessed by a population pharmacokinetics (PPK) model developed using statistically significant covariates identified in a previous PPK analysis plus additional covariates. Data from 3,411 patients who received ipilimumab 0.3–10 mg/kg alone or in combination with niv olumab in 16 clinical trials were analyzed. Ipilimumab CL decreased over time; the ch...
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research
The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immuno-oncology therapies targeting the PD-1/PD-L1 checkpoint. These recommendations are issued as 38 Guideline Statements that address (i) assay development for surgical pathology and cytopathology specimens, (ii) reporting elements, and (iii) quality assurance (including validation/verification, internal quality assurance, and external quality assurance). The intent of...
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Hot Topic Source Type: research
ConclusionsThe RP2D of rSIFN-co was 30ug (1.6  × 107IU) 3x/week for 21days followed by 7 days ’ rest. Anti-tumour activity seen in heavily pre-treated advanced solid tumor patients. especially in HCC. Future plans involve combinations with other immunotherapies.Clinical trial identificationNCT02387307.Legal entity responsible for the studySichuan Huiyang Life Science and Technology Corporation.FundingSichuan Huiyang Life Science and Technology Corporation.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, 5-HTR1B, 5-HTR2B, DRD1, and DRD2 show mRNA overexpression in a broad spectrum of common and rare cancers. 5-HTR2B protein is frequently highly expressed in human cancers, especially on endothelial cells. These findings support further investigation of especially 5HTR2B as a potential treatment target. PMID: 31478179 [PubMed - as supplied by publisher]
Source: Pathology Oncology Research - Category: Pathology Authors: Tags: Pathol Oncol Res Source Type: research
Abstract Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non-small-cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Surveillance imaging in patients with a history of solid organ malignancies has led to increased identification of asymptomatic adrenal masses, which raises clinical ambiguity in patients with known prior or concurrent malignancies. Single adrenal masses (incidentalomas) are found incidentally in 2%-9% of all abdominal CT scans. Adrenal metastases are most commonly seen in renal cell carcinoma, melanoma, lung cancer, colon cancer and lymphoma. The involvement of adrenal gland upstages the disease.
Source: Gastrointestinal Endoscopy - Category: Gastroenterology Authors: Tags: Tuesday abstract Source Type: research
In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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