A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors
Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L, Juan G, Hwang YC, Wong S, Hill JS, Friberg G, LoRusso PM. A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors. Clinical Cancer Research 2010, 16: 5883-5891. PMID: 20947515, DOI: 10.1158/1078-0432.ccr-10-0631.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced solid tumorsPartial responseColorectal cancerStable diseaseSolid tumorsPositron emission tomographic scansHuman death receptor 5Dose-expansion phaseGrade 3 eventsDose-escalation phaseCell lung cancerStandardized uptake valueHuman monoclonal agonist antibodyMonoclonal agonist antibodyDeath receptor 5Week 96Adult patientsAdverse eventsIntravenous dosesMore dosesTumor sizeLung cancerTumor levelsTumor responseMeasurement of conatumumab‐induced apoptotic activity in tumors by fine needle aspirate sampling
Zoog SJ, Y. C, Kaplan‐Lefko P, Hawkins JM, Moriguchi J, Zhou L, Pan Y, Hsu C, Friberg G, Herbst R, Hill J, Juan G. Measurement of conatumumab‐induced apoptotic activity in tumors by fine needle aspirate sampling. Cytometry Part A 2010, 77A: 849-860. PMID: 20623688, DOI: 10.1002/cyto.a.20940.Peer-Reviewed Original ResearchConceptsFine needle aspiratesDeath receptor 5Needle aspiratesNonsmall cell lung cancer patientsCell lung cancer patientsCaspase-3 activationLung cancer patientsTumor necrosis factorCaspase-3Tumor-bearing miceTumor cell deathReceptor therapyPharmacodynamic markersCancer patientsDrug exposureClinical trialsCaspase 3/7 activityNecrosis factorColo205 xenograftsClinical investigationReceptor 5FNA biopsyTumor typesPharmacological impactClinical settingA 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