Population pharmacokinetics and covariate analysis of Sym004, an antibody mixture against the epidermal growth factor receptor, in subjects with metastatic colorectal cancer and other solid tumors

AbstractSym004 is an equimolar mixture of two monoclonal antibodies, futuximab and modotuximab, which non-competitively block the epidermal growth factor receptor (EGFR). Sym004 has been clinically tested for treatment of solid tumors. The present work characterizes the non-linear pharmacokinetics (PK) of Sym004 and its constituent antibodies and investigates two types of covariate models for interpreting the interindividual variability of Sym004 exposure. Sym004 serum concentration data from 330 cancer patients participating in four Phase 1 and 2 trials (n  = 247 metastatic colorectal cancer, n = 87 various types advanced solid tumors) were pooled for non-linear mixed effects modeling. Dose regimens of 0.4–18 mg/kg Sym004 dosed by i.v. infusion weekly or every 2nd week were explored. The PK profiles for futuximab and modotuximab were parall el, and the parameter values for their population PK models were similar. The PK of Sym004 using the sum of the serum concentrations of futuximab and modotuximab was well captured by a 2-compartment model with parallel linear and saturable, Michaelis–Menten-type elimination. The full covariate mod el including all plausible covariates included in a single step showed no impact on Sym004 exposure of age, Asian race, renal and hepatic function, tumor type and previous anti-EGFR treatments. The reduced covariate model contained statistically and potentially clinically significant influences of b o...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

Related Links:

Condition:   Locally Advanced Colon Cancer Intervention:   Combination Product: CAPECITABINE AND OXALIPLATIN Sponsor:   Universidad de León Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Patients With Metastatic Colorectal Cancer Interventions:   Drug: Fluoropyrimidine;   Drug: Bevacizumab Sponsor:   Centre Hospitalier Universitaire Dijon Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Nutrition;   Physical Activity Interventions:   Behavioral: Intervention Physical Activity;   Other: Usual Care Sponsors:   University of North Carolina, Chapel Hill;   University of Texas Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
CONCLUSIONS The findings from network meta-analysis showed that fruquintinib was associated with significant superiority for PFS and DCR compared with TAS-102, but fruquintinib was associated with significantly increased risk for SAEs compared with regorafenib and TAS-102. PMID: 31790382 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Abstract The skin is the largest human organ, comprising the epidermis that is composed of epithelial tissue, the dermis composed of connective tissue, and the innermost subcutaneous tissue. Generally, skin conditions are due to aging and the influence of the external environment, but empirically patients with gastrointestinal diseases are more prone to pruritus and inflammation caused by dry skin. A decrease in the skin barrier function, involving immunocompetent mast cells and oxidative stress, was noted in indomethacin-induced small intestine inflammation, dextran sodium sulfate (DSS)-induced ulcerative colitis...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research
Authors: Xie W, Liu J, Huang X, Wu G, Jeen F, Chen S, Zhang C, Yang W, Li C, Li Z, Ge L, Tang W Abstract Vascular invasion (VI) is an important feature for systemic recurrence and an indicator for the application of adjuvant therapy in colorectal cancer (CRC). Preoperative knowledge of VI is important in determining whether adjuvant therapy is necessary, as well as the adequacy of surgical resection. In the present study, a predictive nomogram for VI in patients with CRC was constructed. The prediction model consisted of 664 eligible patients with CRC, who were divided into a training set (n=468) and a validation s...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Chen C, Gong X, Yang X, Shang X, Du Q, Liao Q, Xie R, Chen Y, Xu J Abstract Estrogen is an important sex steroid hormone which serves an important role in the regulation of a number of biological functions, including regulating bone density, brain function, cholesterol mobilization, electrolyte balance, skin physiology, the cardiovascular system, the central nervous system and female reproductive organs. Estrogen exhibits various functions through binding to its specific receptors, estrogen receptor α, estrogen receptor β and G protein-coupled estrogen receptor 1. In recent years, researchers ha...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Zhu J, Zhao L, Luo B, Sheng W Abstract Colon cancer is a common malignancy, and its morbidity and mortality have been increasing in recent years in China. Shikonin (Shi), a naturally occurring naphthoquinone, exhibits anticancer activity. However, the mechanisms of action of Shi remain unclear. The aim of the present study was to investigate the antitumor mechanism of Shi in colon cancer cells. The effects of different Shi concentrations on the viability of colon cancer cells using MTT, colony formation and wound-healing assays were assessed. Western blot analysis was performed to detect the expression of ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Sena P, Fioresi R, Faglioni F, Losi L, Faglioni G, Roncucci L Abstract Trained pathologists base colorectal cancer identification on the visual interpretation of microscope images. However, image labeling is not always straightforward and this repetitive task is prone to mistakes due to human distraction. Significant efforts are underway to develop informative tools to assist pathologists and decrease the burden and frequency of errors. The present study proposes a deep learning approach to recognize four different stages of cancerous tissue development, including normal mucosa, early preneoplastic lesion,...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, CDK9 may be utilized to evaluate the prognosis and the immune-type of the tumor microenvironment in patients with MSS mCRC. PMID: 31788079 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
More News: Cancer | Cancer & Oncology | Colorectal Cancer | Drugs & Pharmacology | Men | Statistics