Background: JPI-547 is an oral inhibitor of PARP 1/2 and Tankyrase 1/2. JPI-547 demonstrated anti-tumor activity in BRCA-deficient xenograft models as a single-agent and in combination with chemotherapy and immune checkpoint inhibitors. Methods: This is the first in human (FIH) phase I study of JPI-547 in patients (pts) with advanced solid tumors. For the dose escalation phase, a 3+3 design was used with 4 doses from 50 to 200 mg QD on 21-day cycles. Primary objectives were to assess safety and tolerability to determine RP2D, and secondary objectives included pharmacokinetics and preliminary antitumor activities. DLT monitoring period was 21 days. Pharmacodynamics and information of HRR mutation were also explored. For the dose expansion phase, pts with documented pathogenic germline or somatic BRCA/HRR mutations were enrolled to assess the preliminary efficacy and safety. Tumor response (RECIST 1.1) was evaluated every 6 weeks. Centralized germline BRCA testing was conducted to confirm pathogenic gBRCA mutations. Results available at the cut-off date of 31-Dec-2020 are presented. Results: For dose escalation phase, 22 pts were enrolled. JPI-547 was well absorbed with T_max of 0.25-8 h post-dose and apparent half-life of 18-31 h. Mean C_max and AUC increased proportionally (within the dose range of 50-200 mg). PAR level measured from PBMC was 53% inhibited at C_max. One DLTs was observed at 100 mg (elevated ALT, G3) and 200 mg (elevated ALT/AST, G3) respectively. MTD was determined as 200 mg after considering DLTs and myelosuppression observed from cycle 2. RP2D was determined to be 150 mg based on the pharmacokinetic data and safety. Thirteen pts (59.1%) had at least one grade 3/4 TRAE and 12 had dose interruption/reduction due to TRAE. The most common ( > 20%) TRAE were anemia, thrombocytopenia and neutropenia. In dose expansion phase, 40 pts were enrolled, and response was evaluable in 39 pts. The best overall responses were 11 confirmed PR (cPR) and 15 SD with ORR of 28.2% (11/39) and DCR of 64.1 % (25/39). The mPFS was 3.5 mos and mDoR was 3.4 mos. At the time of data cut-off, three pts were ongoing as following response and cancer types: cPR (breast, ATMm, 9.0 mos), cPR (NSCLC, gBRCA2m, 3.8 mos) and SD (breast, gBRCAm, 9.3 mos). Five pts (2 ovarian, 3 breast) previously treated with olaparib and discontinued due to progressive disease were enrolled in this JPI-547 trial and one ovarian cancer pt showed cPR with 37% tumor shrinkage. Conclusions: These results demonstrate that JPI-547 is adequately absorbed with acceptable safety profile. Preliminary efficacy results suggest that JPI-547 monotherapy is effective in pts with BRCA/HRR mutation. Further investigation is warranted in pts with solid tumor including PARP inhibitor resistant cases. Clinical trial information: NCT04335604