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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 phase I,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 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China,Eligible patients for D-Esc 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 (mPFS) 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 (gBRCAMut) (11/43 OC;2/16 BC),mPFS 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.