Rituximab is a monoclonal antibody (mAb) among the top 10 best-selling drugs, with global sales estimated to exceed $7B in 2015. Rituximab is indicated to treat conditions including chronic lymphocytic leukemia (CLL), B-cell non-Hodgkin's lymphoma, and various autoimmune disorders. Population pharmacokinetic studies have revealed considerable differences in the final levels of rituximab found in the blood after a course of therapy, and these levels correlate with therapeutic outcomes.Withcurrentdosingregimens,asubstantialfractionofthepatientsmaynotbereceivingan efficacious dose. During clinical development, laboratory-based tests are used to monitor rituximab levelsinpatients,butthesetestsarenotavailabletophysiciansafterapproval.Currently,thereareno point-of-care(POC)testsavailabletomonitorthelevelsofrituximabinpatients.Thegoalofthisproject istodeveloplowcostPOCdevicesthatprovideaquantitativemeasureofrituximablevelsinblood. Thesetestswillhelpphysicianspersonalizethedosingofpatientsandidentifyearlyrituximabtreatment failuresresultingfromlowdruglevels.Ourcoreenablingtechnologyplatformisbasedonmimetope peptides,termedVeritopesTM,thatmimicthecognateligandofagivenmAbandspecificallybindatthe antigen binding site. VeritopesTM are cheap, robust, and simple to integrate into lateral flow immunoassay (LFA) that then enables inexpensive POC testing. In preliminary studies, we demonstrated the feasibility of VeritopeTM-based LFA for the qualitative detection of rituximab, trastuzumab,andbevacizumablevelsinbiologicfluidsaswellasthepotentialtodevelopquantitative tests.InthisPhaseIIproject,wewillcompletethedevelopmentofaCLIA-waivablerituximabmonitoring testthatcanbeperformedatthePOCfromasingledropofblood.WewillintegratetheLFAstripsinto single-use, disposable digital LFA reader devices that can provide quantitative analysis of the test strips.ThesedeviceswillbevalidatedinaclinicaltrialinpartnershipwithUCSDMooresCancerCenter usingbloodsamplesfrompatientstreatedwithrituximab.ThedatageneratedduringthisPhaseIIstudy willbeincorporatedinourtechnicaldatapackagetosubmittoFDAforclearanceofourdevice,which willbethefirstFDAcleareddeviceforbiologicdrugmonitoringatthePOC. Thisinnovativeproductwillfulfillofanunmetclinicalneedforarapid,costeffective,andaccuratedose monitoringassay.Precisiondosingthroughdata-driven,personalizedregimenswillimprovetreatment outcomesandmaximizetheefficientuseofthisandothermonoclonalantibodytherapeutics.
Summary Rituximabisamonoclonalantibodyusedtotreatmanytypesofcancerandautoimmunedisorders,but there is growing evidence that some patients are not receiving enough of this agent when given standard doses. This project will finalize development and fully validate simple lateral flow assay devicesthatcanmeasurewithinminuteshowmuchrituximabispresentinapatient?sblood.
