Clinical Research Alliance/Weill Cornell Medicine, New York, NY, USA.
4th Department of Internal Medicine - Haematology, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Czech Republic.
Leuk Lymphoma. 2021 Feb;62(2):368-376. doi: 10.1080/10428194.2020.1832660. Epub 2020 Nov 3.
Parsaclisib, a potent, highly selective, next-generation PI3Kδ inhibitor, was evaluated as monotherapy in CITADEL-202 (NCT02998476), an open-label, multicenter, phase 2 study in patients with relapsed or refractory diffuse large B-cell lymphoma. Patients enrolled into 2 groups (A, Bruton tyrosine kinase [BTK] inhibitor naïve, = 55; B, BTK inhibitor experienced, = 5) received oral parsaclisib 20 mg once daily for 8 weeks, then 20 mg once weekly while deriving benefit. The futility boundary was crossed at the interim analysis of Group A, resulting in a negative study. Parsaclisib monotherapy demonstrated an objective response rate (ORR) of 25.5% (8 complete metabolic responses/6 partial metabolic responses) and a median duration of response of 6.2 months. ORR in Group B was 20.0% (1 complete metabolic response). Parsaclisib monotherapy demonstrated manageable toxicities with no new safety signals reported. Further evaluation of parsaclisib in combination with standard therapies and active investigational agents is underway.
帕萨昔布是一种强效、高度选择性的下一代 PI3Kδ 抑制剂，曾在 CITADEL-202 （NCT02998476）中作为单药疗法进行评估，这是一项开放标签、多中心、2 期临床试验，招募了复发或难治性弥漫性大 B 细胞淋巴瘤患者。患者分为 2 组（A 组：BTK 抑制剂初治，n=55；B 组：BTK 抑制剂经治，n=5）接受口服帕萨昔布 20mg，每日 1 次，连用 8 周，随后 20mg，每周 1 次，直至获益。A 组的中期分析结果达到无效边界，导致该研究结果为阴性。帕萨昔布单药治疗的客观缓解率（ORR）为 25.5%（8 例完全代谢缓解/6 例部分代谢缓解），缓解持续时间的中位数为 6.2 个月。B 组的 ORR 为 20.0%（1 例完全代谢缓解）。帕萨昔布单药治疗的毒性可管理，未报告新的安全性信号。正在进行帕萨昔布联合标准疗法和活性研究药物的进一步评估。
