التفاصيل البيبلوغرافية
| العنوان: |
Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer. |
| المؤلفون: |
Duska, Linda R., Zamarin, Dmitriy, Hamilton, Erica, Oza, Amit, Fleming, Gini, Spira, Alexander, Yeku, Oladapo O., Richardson, Debra L., Walling, Jackie, Inokuchi, Kerry, Matusow, Bernice, Bollag, Gideon, Swisher, Elizabeth M. |
| المصدر: |
JCO Precision Oncology; 10/5/2023, Vol. 7, p1-11, 11p |
| مصطلحات موضوعية: |
OVARIAN epithelial cancer, OVARIAN cancer, GYNECOLOGIC cancer, PROTEIN domains |
| مستخلص: |
PURPOSE: The Bromodomain and Extra-Terminal (BET) domain proteins facilitate the development of many human cancers via epigenetic regulation. BET inhibitors may be effective in reversing platinum resistance in ovarian cancer (OC) and may generate synthetic lethality with ARID1A loss. PLX2853 is an orally active, small-molecule inhibitor of BET bromodomain-mediated interactions that exhibits low nanomolar potency in blocking all four BET family members. METHODS: We conducted a multicenter and open-label study with two parallel arms: a phase IIa study of PLX2853 monotherapy in patients with advanced gynecologic malignancies with an ARID1A mutation and a phase Ib/IIa combination study of PLX2853 plus carboplatin in women with platinum-resistant OC. The primary objectives were safety and tolerability for phase Ib and efficacy for both phase IIa portions. Thirty-four of 37 enrolled patients completed at least one post-baseline response assessment. RESULTS: Of the 14 evaluable patients on the monotherapy arm, 1 (7.1%) achieved a best overall response of partial response (PR), 5 (35.7%) had stable disease (SD), and 8 (57.1%) had progressive disease (PD). Of the 20 evaluable patients on the combination arm, 1 (5.0%) had PR, 9 (45.0%) had SD, and 10 (50%) had PD. CONCLUSION: This study confirmed the safety profile of PLX2853 and demonstrated the feasibility of combination with carboplatin. Although these results did not meet the prespecified response criteria, evidence of clinical activity highlights the rationale for further exploration of BET inhibitors in patients with ARID1A -mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway. [ABSTRACT FROM AUTHOR] |
|
Copyright of JCO Precision Oncology is the property of American Society of Clinical Oncology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
