BACKGROUND: Venadaparib, a novel poly (ADP-ribose) polymerase (PARP) inhibitor, has demonstrated high PARP-1/2 selectivity over other PARP family members and exhibited strong PARP-trapping activity, effectively inhibiting tumor growth in homologous recombination deficient (HRD) cancer in vitro and in vivo. METHODS: This phase 1, dose-finding study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and anticancer efficacy of venadaparib as monotherapy in patients with advanced solid tumors that progressed after standard-of-care therapy. The study employed a conventional 3+3 design, with doses ranging from 2 mg/d to 240 mg/d. RESULTS: Among the 32 enrolled patients, the most common tumor types were breast (16 patients) and ovarian (12 patients) cancers. No dose-limiting toxicities (DLTs) were observed up to 240 mg/d. The most frequent grade 3 or 4 adverse events were anemia (50%), neutropenia (22%) and thrombocytopenia (6%). Tumor shrinkage by Response Evaluation Criteria in Solid Tumours (RECIST) was observed at doses ≥ 40 mg/d, regardless of BRCA mutation status.Two partial responses out of four ovarian cancer patients receiving venadaparib ≥ 40 mg/d were reported. Clinical benefit, defined as stable disease or partial response, was observed at the lowest tested dose. Venadaparib exhibited ≥ 90% PAR inhibitory effect in pharmacodynamic analysis from 10 mg/d based on tumor samples. The recommended phase 2 dose (RP2D) was defined as 160 mg once daily. CONCLUSIONS: Further studies are warranted to explore efficacy and safety of venadaparib in other tumor types and in combination with various agents, as well as to explore relevant biomarkers. (ClinicalTrials.gov ID: NCT03317743).