Background: SC10914 is a highly selective inhibitor of PARP enzymes, including PARP1 and PARP2. SC10914 has a similar structure with olaparib. We conducted a phase I study to assess the safety, tolerability, PK/PD and preliminary efficacy of SC10914 in patients with advanced solid tumors. Methods: This is a phase I dose-escalation study with 3+3 design, we enrolled patients at 4 sites in China. Eligible patients were diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists; had measurable disease; had adequate organ function. Patients received SC10914 daily at ten escalating doses from 30 mg QD to 500 mg TID in a 28-day cycle. We obtained blood for PK and CA125 assessments. Toxic effects were assessed by CTCAE 4.03 criteria and tumour responses ascribed by RECIST 1.1 and CA125 was assessed by GCIG criteria. Results: As of January 2020, 52 patients were enrolled, of which 14 were males and 38 were females. Ten doses were escalated to 500mg TID, and no DLT was observed, and MTD was not obtained. The incidence of grade 3/4 AEs and SAEs that were related to SC10914 were 34.6% (18/52) and 13.5% (7/52). Grade 3/4 adverse reaction happened in at least two patients were anaemia/reduced hemoglobin (10/52, 19.2%), decreased WBC count (5/52, 9.6%), neutropenia (3/52, 5.8%), thrombocytopenia (2/52, 3.8%), and decreased lymphocyte count (2/52, 3.8%). A total of 17 gBRCAm evaluable ovarian cancer patients were enrolled, 6 of them had PR, the ORR was 35.3% (6/17). 10 gBRCAm ovarian cancer patients were enrolled in TID groups (including 2 patients who received BID doses at the beginning and changed to 300 mg TID dose after several cycles of treatment), 5 of them had PR, the ORR was 50% (5/10). The ORR of 400 mg TID group was 66.7%(4/6). PK data showed that the exposure of SC10914 was increased with dose increasing at the dose of 30 mg to 250 mg. The half-life of SC10914 was about 2-5 hours. Conclusions: SC10914 was safe in patients with advanced solid tumors. The main toxicity was blood-related adverse reactions. SC10914 was effective in gBRCAm ovarian cancer patients. 400 mg TID might be RP2D. Clinical trial information: NCT02940132