0000000001051546
AUTHOR
Carlos Gomez-roca
Phase I Pharmacokinetic and Pharmacodynamic Dose-Escalation Study of RG7160 (GA201), the First Glycoengineered Monoclonal Antibody Against the Epidermal Growth Factor Receptor, in Patients With Advanced Solid Tumors
Purpose We conducted a phase I dose-escalation study to characterize the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201), a humanized and glycoengineered immunoglobulin G1 anti–epidermal growth factor receptor (EGFR) monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity. Patients and Methods Seventy-five patients with advanced EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered every week, every 2 weeks, or every 3 weeks. Dose escalation followed a three-plus-three trial design. Results No maximum-tolerated dose was reached for any dosing schedule. Common adverse events (AEs) included rash (80% of patien…
Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring
BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, im…
Open-label, multicentre expansion cohort to evaluate imgatuzumab in pre-treated patients with KRAS-mutant advanced colorectal carcinoma.
Abstract Aim Imgatuzumab (GA201) is a novel anti-epidermal growth factor receptor (anti-EGFR) antibody glycoengineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated the efficacy of imgatuzumab in patients with EGFR-positive, KRAS -mutant advanced colorectal cancer. Methods Patients received single-agent imgatuzumab (1400 mg on day 1 and 8 followed by q2W) as third line therapy in an open-label, multicentre, non-randomised, expansion study. The primary end-point was tumour response. Pre- and on-treatment biopsies and blood samples were investigated for biomarkers related to imgatuzumab’s believed mechanism of action (MoA). Results 25 patients were treated…