{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:32:35Z","timestamp":1783355555107,"version":"3.54.6"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Venadaparib, a novel poly (ADP\u2010ribose) polymerase (PARP) inhibitor, has demonstrated high PARP\u20101\/2 selectivity over other PARP family members and exhibited strong PARP\u2010trapping activity, effectively inhibiting tumor growth in homologous recombination deficient (HRD) cancer in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase 1, dose\u2010finding study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and anticancer efficacy of venadaparib as monotherapy in patients with advanced solid tumors that progressed after standard\u2010of\u2010care therapy. The study employed a conventional 3+3 design, with doses ranging from 2 mg\/d to 240 mg\/d.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 32 enrolled patients, the most common tumor types were breast (16 patients) and ovarian (12 patients) cancers. No dose\u2010limiting 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 \u2265 40 mg\/d, regardless of BRCA mutation status.Two partial responses out of four ovarian cancer patients receiving venadaparib \u2265 40 mg\/d were reported. Clinical benefit, defined as stable disease or partial response, was observed at the lowest tested dose. Venadaparib exhibited \u2265 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70576","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T11:46:26Z","timestamp":1739447186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["First\u2010In\u2010Human Dose Finding Study of Venadaparib (<scp>IDX<\/scp>\u20101197), a Potent and Selective <scp>PARP<\/scp> Inhibitor, in Patients With Advanced Solid Tumors"],"prefix":"10.1002","volume":"14","author":[{"given":"Sung\u2010Bae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Oncology, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyun\u2010Seop","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology &amp; Therapeutics, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Lyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Sik","family":"Lee","sequence":"additional","affiliation":[{"name":"Idience Co. 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