靶向VEGF和HGF的首个DARPin

SCI

24December

First-in-HumanPhaseIStudyofMP,aFirst-in-ClassDARPinDrugCandidateTargetingVEGFandHGF,inPatientsWithAdvancedSolidTumors（JClinOncol;IF：32.）

BAIRDRD,LINOSSIC,MIDDLETONM,etal.First-in-HumanPhaseIStudyofMP,aFirst-in-ClassDARPinDrugCandidateTargetingVEGFandHGF,inPatientsWithAdvancedSolidTumors[J].JClinOncol,,Jco.

PURPOSE目的

Afirst-in-humanstudywasperformedwithMP,aDARPindrugcandidate.MPspecificallyinhibitsbothvascularendothelialgrowthfactor(VEGF)andhepatocytegrowthfactor(HGF)withtheaimofdisruptingthetumormicroenvironment.

对DARPin候选药物MP进行了首次人体研究。MP特异性地抑制血管内皮生长因子(VEGF)和肝细胞生长因子(HGF)，目的是破坏肿瘤微环境。

PATIENTSANDMETHODS患者及方法

Amulticenter,open-label,repeated-dose,phaseIstudywasconductedtoassessthesafety,tolerability,andpharmacokineticsofMPin45patientswithadvancedsolidtumors.Inthedoseescalationpart,24patientsreceivedMPasa3-hourinfusiononceevery2weeksatfivedifferentdoselevels(0.5-12mg/kg).Oncethemaximumtolerateddose(MTD)wasestablished,21patientsweretreatedwitha1-hourinfusion(n=13,8mg/kg,onceevery2weeksandn=8,12mg/kg,onceevery3weeks)ofMPinthedoseconfirmationcohorts.

对45例晚期实体肿瘤患者进行了一项多中心、开放、重复给药的I期研究，以评估MP的安全性、耐受性和药代动力学。在剂量递增部分，24例患者接受5种不同剂量(0.5~12mg/kg)的MP静脉滴注，每2周1次，每次3h。在确定最大耐受量(MTD)后，21例患者在剂量确认队列中给予MP1h静脉滴注(n=13，8mg/kg，每2周1次；n=8，12mg/kg，每3周1次)。

RESULTS结果

Inthedose-escalationcohort,patientstreatedwith12mg/kgMPonceevery2weeksexperienceddose-limitingtoxicities.Therefore,MTDwas8mg/kgonceevery2weeksor12mg/kgonceevery3weeks.Themost