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Abstract：
UNASSIGNED: Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit in patients with relapsed/refractory (R/R) B-cell malignancies. In this phase 2 study (CITADEL-205; NCT03235544, EudraCT 2017-003148-19), the efficacy and safety of parsaclisib was evaluated in patients with R/R mantle cell lymphoma (MCL).
UNASSIGNED: Patients ≥18 years old with pathologically confirmed R/R MCL and prior treatment with 1-3 systemic therapies, with (cohort 1) or without (cohort 2) previous Bruton kinase inhibitor (BTKi) treatment, received oral parsaclisib 20 mg once-daily (QD) for 8 weeks, then either parsaclisib 20 mg once-weekly (weekly dosing group [WG]) or parsaclisib 2.5 mg QD (daily dosing group [DG]). The primary endpoint was objective response rate (ORR).
UNASSIGNED: At the primary analysis data cutoff on January 15, 2021, 53 patients in cohort 1 (BTKi-experienced) (WG, n = 12; DG: n = 41) and 108 patients in cohort 2 (BTKi-naive) (WG, n = 31; DG: n = 77) had received parsaclisib monotherapy. The BTKi-experienced cohort was closed after an interim analysis demonstrated limited clinical benefit. In the BTKi-naive cohort, the ORR (95% CI) for DG (dosing selected for further study) was 70.1% (58.6%-80.0%), with a complete response rate (95% CI) of 15.6% (8.3%-25.6%) and a median duration of response (95% CI) of 12.1 (9.0-not evaluable) months. Treatment-emergent adverse events (TEAEs) occurred among 90.7% (98/108) of all treated patients in the BTKi-naive cohort. Grade ≥3 TEAEs occurred among 62.0% (67/108) of patients, including diarrhoea (13.9%, 15/108) and neutropenia (8.3%, 9/108). Parsaclisib interruption, reduction, or discontinuation due to TEAEs occurred among 47.2% (51/108), 8.3% (9/108), and 25.0% (27/108) of patients, respectively. Fatal TEAEs were experienced by six patients and determined to be treatment-related in one patient.
UNASSIGNED: Parsaclisib, a potent, highly selective, PI3Kδ inhibitor demonstrated meaningful clinical benefits and a manageable safety profile (25.0% discontinuation rate, low incidences of individually reported grade ≥3 or serious adverse events) in R/R MCL patients with no prior BTKi therapy. Limited clinical benefit was observed with parsaclisib monotherapy in patients who had previously received BTKi treatment. Future development of PI3K inhibitors for NHL will require further investigation of dose optimisation to improve safety and long-term survival.
UNASSIGNED: Incyte Corporation.
UNASSIGNED: Patients ≥18 years old with pathologically confirmed R/R MCL and prior treatment with 1-3 systemic therapies, with (cohort 1) or without (cohort 2) previous Bruton kinase inhibitor (BTKi) treatment, received oral parsaclisib 20 mg once-daily (QD) for 8 weeks, then either parsaclisib 20 mg once-weekly (weekly dosing group [WG]) or parsaclisib 2.5 mg QD (daily dosing group [DG]). The primary endpoint was objective response rate (ORR).
UNASSIGNED: At the primary analysis data cutoff on January 15, 2021, 53 patients in cohort 1 (BTKi-experienced) (WG, n = 12; DG: n = 41) and 108 patients in cohort 2 (BTKi-naive) (WG, n = 31; DG: n = 77) had received parsaclisib monotherapy. The BTKi-experienced cohort was closed after an interim analysis demonstrated limited clinical benefit. In the BTKi-naive cohort, the ORR (95% CI) for DG (dosing selected for further study) was 70.1% (58.6%-80.0%), with a complete response rate (95% CI) of 15.6% (8.3%-25.6%) and a median duration of response (95% CI) of 12.1 (9.0-not evaluable) months. Treatment-emergent adverse events (TEAEs) occurred among 90.7% (98/108) of all treated patients in the BTKi-naive cohort. Grade ≥3 TEAEs occurred among 62.0% (67/108) of patients, including diarrhoea (13.9%, 15/108) and neutropenia (8.3%, 9/108). Parsaclisib interruption, reduction, or discontinuation due to TEAEs occurred among 47.2% (51/108), 8.3% (9/108), and 25.0% (27/108) of patients, respectively. Fatal TEAEs were experienced by six patients and determined to be treatment-related in one patient.
UNASSIGNED: Parsaclisib, a potent, highly selective, PI3Kδ inhibitor demonstrated meaningful clinical benefits and a manageable safety profile (25.0% discontinuation rate, low incidences of individually reported grade ≥3 or serious adverse events) in R/R MCL patients with no prior BTKi therapy. Limited clinical benefit was observed with parsaclisib monotherapy in patients who had previously received BTKi treatment. Future development of PI3K inhibitors for NHL will require further investigation of dose optimisation to improve safety and long-term survival.
UNASSIGNED: Incyte Corporation.
摘要：
■Parsaclisib是一种有效且高度选择性的PI3Kδ抑制剂，已在患有复发性/难治性（R/R）B细胞恶性肿瘤的患者中显示出临床益处。在此第2阶段研究（CITADEL-205；NCT03235544，EudraCT2017-003148-19），在R/R套细胞淋巴瘤(MCL)患者中评估了parsaclisib的疗效和安全性.
■年龄≥18岁的患者，经病理证实为R/RMCL，先前接受过1-3种全身治疗，（队列1）或不（队列2）先前的布鲁顿激酶抑制剂（BTKi）治疗，口服parsaclisib20mg，每日一次（QD），持续8周，然后是parsaclisib20mg每周一次（每周给药组[WG]）或parsaclisib2.5mgQD（每日给药组[DG]）。主要终点是客观缓解率（ORR）。
■在2021年1月15日的主要分析数据截止时，队列1中的53名患者（经历了BTKi）（WG，n=12；DG：n=41）和队列2中的108名患者（BTKi-naive）（WG，n=31；DG：n=77）已接受帕拉萨利西布单一疗法。有BTKi经验的队列在中期分析显示临床获益有限后关闭。在BTKi天真的队列中，DG（选择用于进一步研究的剂量）的ORR（95％CI）为70.1％（58.6％-80.0％），完全缓解率（95％CI）为15.6％（8.3％-25.6％），中位缓解持续时间（95％CI）为12.1（9.0-不可评估）月。在BTKi-naive队列中，90.7%(98/108)的所有接受治疗的患者发生治疗引起的不良事件(TEAE)。62.0%(67/108)的患者发生≥3级TEAE，包括腹泻(13.9%,15/108）和中性粒细胞减少（8.3%，9/108)。Parsaclisib中断，reduction,或因TEAE而停药的发生率为47.2%(51/108)，8.3%（9/108），25.0%(27/108)的患者，分别。六名患者经历了致命的TEAE，并确定一名患者与治疗相关。
■Parsaclisib，一个强大的，高度选择性,PI3Kδ抑制剂显示了有意义的临床益处和可管理的安全性（25.0％的停药率，在之前没有BTKi治疗的R/RMCL患者中，单独报告的≥3级或严重不良事件的发生率较低）。在先前接受BTKi治疗的患者中，使用parsaclib单一疗法观察到有限的临床益处。用于NHL的PI3K抑制剂的未来发展将需要进一步研究剂量优化以提高安全性和长期生存率。
■Incyte公司。
■年龄≥18岁的患者，经病理证实为R/RMCL，先前接受过1-3种全身治疗，（队列1）或不（队列2）先前的布鲁顿激酶抑制剂（BTKi）治疗，口服parsaclisib20mg，每日一次（QD），持续8周，然后是parsaclisib20mg每周一次（每周给药组[WG]）或parsaclisib2.5mgQD（每日给药组[DG]）。主要终点是客观缓解率（ORR）。
■在2021年1月15日的主要分析数据截止时，队列1中的53名患者（经历了BTKi）（WG，n=12；DG：n=41）和队列2中的108名患者（BTKi-naive）（WG，n=31；DG：n=77）已接受帕拉萨利西布单一疗法。有BTKi经验的队列在中期分析显示临床获益有限后关闭。在BTKi天真的队列中，DG（选择用于进一步研究的剂量）的ORR（95％CI）为70.1％（58.6％-80.0％），完全缓解率（95％CI）为15.6％（8.3％-25.6％），中位缓解持续时间（95％CI）为12.1（9.0-不可评估）月。在BTKi-naive队列中，90.7%(98/108)的所有接受治疗的患者发生治疗引起的不良事件(TEAE)。62.0%(67/108)的患者发生≥3级TEAE，包括腹泻(13.9%,15/108）和中性粒细胞减少（8.3%，9/108)。Parsaclisib中断，reduction,或因TEAE而停药的发生率为47.2%(51/108)，8.3%（9/108），25.0%(27/108)的患者，分别。六名患者经历了致命的TEAE，并确定一名患者与治疗相关。
■Parsaclisib，一个强大的，高度选择性,PI3Kδ抑制剂显示了有意义的临床益处和可管理的安全性（25.0％的停药率，在之前没有BTKi治疗的R/RMCL患者中，单独报告的≥3级或严重不良事件的发生率较低）。在先前接受BTKi治疗的患者中，使用parsaclib单一疗法观察到有限的临床益处。用于NHL的PI3K抑制剂的未来发展将需要进一步研究剂量优化以提高安全性和长期生存率。
■Incyte公司。
