2011
Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours
Pan Y, Xu R, Peach M, Huang CP, Branstetter D, Novotny W, Herbst RS, Eckhardt SG, Holland PM. Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours. British Journal Of Cancer 2011, 105: 1830-1838. PMID: 22033270, PMCID: PMC3251880, DOI: 10.1038/bjc.2011.456.Peer-Reviewed Original ResearchConceptsCell death markersAdvanced tumorsPharmacodynamic biomarkersApoptotic markersPhase 1a studyPhase 1a trialDeath receptors DR4Colo205 tumorsSerum 8Patients 24Active caspase-3Patient seraColo205 xenograftsEvidence of activitySubsequent cell deathCytokeratin 18PatientsTransient increaseDulanerminReceptors DR4TumorsCaspase-3SerumCaspase-3/7Significant increase
2010
A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies
Camidge DR, Herbst RS, Gordon MS, Eckhardt SG, Kurzrock R, Durbin B, Ing J, Tohnya TM, Sager J, Ashkenazi A, Bray G, Mendelson D. A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies. Clinical Cancer Research 2010, 16: 1256-1263. PMID: 20145186, DOI: 10.1158/1078-0432.ccr-09-1267.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade 3 transaminase elevationHuman IgG1 monoclonal antibodyPhase I safetyDose-escalation designDose-dependent increaseDeath receptor 5Different tumor typesIgG1 monoclonal antibodyCohort expansionTransaminase elevationI safetyMost patientsObjective responseTrough concentrationsAdverse eventsEscalation designMultiple dosesMinor responseEfficacious concentrationsOvarian cancerEvidence of activityPharmacokinetic analysisReceptor 5Human studies