PhaseⅠdose-escalation and expansion study of PARP inhibitor,fluzoparib(SHR3162),in patients with advanced solid tumors

Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-Esc and D-Ex)trial in patients with advanced solid cancer.Methods:This was a 3+3 phaseⅠD-Esc trial with a 3-level D-Ex at 5 hospitals in China.Eligible patients for DEsc had advanced solid tumors refractory to standard therapies,and D-Ex enrolled patients with ovarian cancer(OC).Fluzoparib was administered orally once or twice daily(bid)at 11 dose levels from 10 to 400 mg/d.Endpoints included dose-finding,safety,pharmacokinetics,and antitumor activity.Results:Seventy-nine patients were enrolled from March,2015 to January,2018[OC(47,59.5%);breast cancer(BC)(16,20.3%);colorectal cancer(8,10.1%),other tumors(8,10.1%)];48 patients were treated in the D-Esc arm and 31 in the D-Ex arm.The maximum tolerated dose(MTD)was 150 mg bid,with a half-life of 9.14 h.Grade 3/4 adverse events included anemia(7.6%)and neutropenia(5.1%).The objective response rate(ORR)was 30%(3/10)in patients with platinum-sensitive OC and 7.7%(1/13)in patients with BC.Among patients treated with fluzoparib≥120 mg/d,median progression-free survival(m PFS)was 7.2[95%confidence interval(95%CI),1.8-9.3]months in OC,9.3(95%CI,7.2-9.3)months in platinum-sensitive OC,and 3.5(range,2.0-28.0)months in BC.In patients with germline BC susceptibility gene mutation(g BRCAMut)(11/43 OC;2/16 BC),m PFS was 8.9 months for OC(range,1.0-23.2;95%CI,1.0-16.8)and 14 and 28 months for BC(those two patients both also had somatic BRCAMut).Conclusions:The MTD of fluzoparib was 150 mg bid in advanced solid malignancies.Fluzoparib demonstrated single-agent antitumor activity in BC and OC,particularly in BRCAMut and platinum-sensitive OC.

Polymer “Tape”-Assisted Ball-Milling Method Fabrication Few-Atomic-Layered Bismuth for Improving K^(+)/Na^(+)Storage

Few-layered 2D analogs exhibit new physical/chemical properties,leading to a strong research interest and broad areas of application.Recently,lots of methods(such as ultrasonic and electrochemical methods)have already used to prepared 2D materials.However,these methods suffer from the drawbacks of low yield,high cost,or precarious state,which limit the largescale applications.Inspired by the famous Scotch tape method,we develop a ball-milling with polymer"tape"method,fabricating few-atomic-layered material,showing the high-yield,low-cost,and much stability.As electrode material,ultrathin 2D materials can shorten the ion transfer pathway,contributing to the development of high-power batteries.Meanwhile,fewatomic-layered structure can expose more active sites to increase their capacity,showing special energy storage mechanism.We use the as-prepared few-atomic-layered Bi(FALB)and reduced oxide graphene composites as the anode for potassium/sodium-ion batteries(KIBs/NIBs).The sample achieves a high reversible capacity of 395 m Ah g^(-1)for KIBs,of which FALB contributes 438 m Ah g^(-1)(higher than the theoretical capacity of Bi,386 m Ah g^(-1)),and it carries outstanding cycle and rate performance in KIBs/NIBs.