First‐In‐Human Dose Finding Study of Venadaparib ( IDX ‐1197), a Potent and Selective PARP Inhibitor, in Patients With Advanced Solid Tumors
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Le résumé fourni par la source
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).
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- First‐In‐Human Dose Finding Study of Venadaparib (<scp>IDX</scp>‐1197), a Potent and Selective <scp>PARP</scp> Inhibitor, in Patients With Advanced Solid Tumors
- Date Crossref
- 01/02/2025
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Ulsan College Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
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Asan Medical Center pays non établi dans la noticeÉtablissement de santé
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University of Ulsan pays non établi dans la noticeUniversité ou école supérieure
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Ildong (South Korea) pays non établi dans la noticeEntreprise
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Idience Co. Ltd. Seoul Republic of Korea pays non établi dans la noticeEntreprise
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Idience Inc. Irvine California USA pays non établi dans la noticeEntreprise
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Ildong Pharmaceutical Co. Ltd Gyeonggi‐do Republic of Korea pays non établi dans la noticeEntreprise
Department of Oncology — Ulsan College, Asan Medical Center et University of Ulsan, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.