Eli Lilly announced results from the Phase III BRUIN CLL-321 trial evaluating pirtobrutinib, a non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor in adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor.

礼来公司宣布了三期BRUIN CLL-321试验的结果，该试验评估了非共价（可逆）布鲁顿酪氨酸激酶（BTK）抑制剂pirtobrutinib在先前接受过共价BTK抑制剂治疗的成人慢性淋巴细胞白血病或小淋巴细胞淋巴瘤（CLL/SLL）患者中的效果。

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The study's primary endpoint of progression-free survival (PFS) was met at primary analysis, demonstrating pirtobrutinib was superior to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR), based on independent review committee (IRC) assessment. Today's updated results corresponding to the final prespecified analysis, demonstrate consistent improvement in PFS for patients treated with pirtobrutinib, with a reduction in risk of relapse, disease or death by 46% compared to IdelaR or BR.

研究的主要终点无进展生存期（PFS）在初步分析时已经达到，证明根据独立审查委员会（IRC）评估，皮托布鲁替尼优于研究者选择的艾代拉利司加利妥昔单抗（IdelaR）或苯达莫司汀加利妥昔单抗（BR）。今天更新的结果对应于最终预设分析，显示接受皮托布鲁替尼治疗的患者PFS持续改善，与IdelaR或BR相比，复发、疾病进展或死亡的风险降低了46%。

These data will be presented in an oral presentation at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition..

这些数据将在第66届美国血液学会（ASH）年会暨展览会上进行口头报告。

'These results demonstrate the ability of pirtobrutinib to deliver clinically meaningful outcomes in a post-covalent BTK inhibitor setting, which is especially remarkable given the poor prognosis for the patient population enrolled in BRUIN CLL-321,' said Jeff Sharman, M.D., Disease Chair, Lymphoma Research Executive Committee, SCRI at Willamette Valley Cancer Institute and Research Center, and one of the principal investigators of the BRUIN CLL-321 trial.

“这些结果证明了pirtobrutinib在共价BTK抑制剂治疗后的环境中提供具有临床意义的结果的能力，鉴于参与BRUIN CLL-321试验的患者群体预后较差，这一点尤其显著，”BRUIN CLL-321试验的主要研究者之一、SCRI淋巴瘤研究执行委员会主席、威拉米特谷癌症研究所和研究中心的杰夫·沙尔曼医学博士表示。

'These data also show that pirtobrutinib can significantly prolong the time to next treatment with a median of approximately two years. Coupled with the safety results, the BRUIN CLL-321 data are important as we consider treatment sequencing for this setting.'.

“这些数据还表明，pirtobrutinib可以显著延长下一次治疗的时间，中位时间约为两年。结合安全性结果，BRUIN CLL-321数据在我们考虑此情况下的治疗顺序时非常重要。”

BRUIN CLL-321

BRUIN CLL-321

enrolled 238 patients who were randomized to receive pirtobrutinib monotherapy (n=119) or investigator's choice of IdelaR or BR (n=119). Patients across both arms received a median of three prior lines of therapy, with all patients having received at least one prior covalent BTK inhibitor. Approximately half of the patients had also received a venetoclax-containing regimen.

共纳入238例患者，随机接受pirtobrutinib单药治疗（n=119）或研究者选择的IdelaR或BR（n=119）。两组患者既往接受治疗的中位线数为三线，所有患者均至少接受过一种共价BTK抑制剂治疗。约一半的患者还接受过含venetoclax的治疗方案。

Reflective of the poor prognosis of patients enrolled in this study, a high proportion of patients presented with high-risk features indicative of aggressive disease, including TP53 mutation and/or 17p deletion, unmutated IGHV status and complex karyotype..

反映本研究中患者预后较差，很大比例的患者表现出高风险特征，提示侵袭性疾病，包括TP53突变和/或17p缺失、未突变的IGHV状态以及复杂核型。

Efficacy results are based on IRC assessment of the intent-to-treat (ITT) population and utilize an Aug. 29, 2024 data cutoff date. Crossover to the pirtobrutinib arm was allowed after IRC-confirmed disease progression. At median follow-up of approximately 19 months, median PFS was 14.0 months for the pirtobrutinib arm compared to 8.7 months for the control arm (HR=0.54 [95% CI, 0.39-0.75]).

疗效结果基于独立审查委员会（IRC）对意向治疗（ITT）人群的评估，并采用截至2024年8月29日的数据。在IRC确认疾病进展后，允许交叉到pirtobrutinib组。在约19个月的中位随访时间时，pirtobrutinib组的中位无进展生存期（PFS）为14.0个月，而对照组为8.7个月（风险比=0.54 [95%置信区间，0.39-0.75]）。

PFS results were consistent across key subgroups associated with a poor prognosis, including patients who received prior venetoclax and those with TP53 mutations and/or 17p deletions, unmutated IGHV status and complex karyotype..

无进展生存期结果在与预后不良相关的关键亚组中保持一致，包括之前接受过维奈托克治疗的患者以及那些具有TP53突变和/或17p缺失、未突变IGHV状态和复杂核型的患者。

Pirtobrutinib also demonstrated clinically meaningful improvements in other secondary endpoints such as investigator-assessed PFS (median PFS: 15.3 vs. 9.2 months; HR=0.48 [95% CI, 0.34-0.67]), event-free survival (EFS) (median EFS: 14.1 vs. 7.6 months; HR=0.39 [95% CI, 0.28-0.53]), and time to next treatment (TTNT) or death (median TTNT: 23.9 vs.

Pirtobrutinib还在其他次要终点上显示出具有临床意义的改善，例如研究者评估的PFS（中位PFS：15.3个月 vs. 9.2个月；HR=0.48 [95% CI，0.34-0.67]）、无事件生存期（EFS）（中位EFS：14.1个月 vs. 7.6个月；HR=0.39 [95% CI，0.28-0.53]），以及至下次治疗（TTNT）或死亡的时间（中位TTNT：23.9个月 vs.）。

10.9 months; HR=0.37 [95% CI, 0.25-0.52]). Specifically, among patients in the control arm who were eligible for crossover, 76% (n=50/66) crossed over to receive pirtobrutinib. Multiple analyses that adjust for the effect of crossover demonstrate trends in favor of pirtobrutinib (Inverse Probability Censored Weighting methodology: HR= 0.89 [95% CI, 0.52-1.53]; two-stage Accelerated Failure Time methodology: HR=0.77 [95% CI, 0.45-1.26])..

10.9个月；HR=0.37 [95% CI, 0.25-0.52]）。具体而言，在对照组中符合交叉条件的患者中，76%（n=50/66）交叉接受pirtobrutinib治疗。多种调整交叉效应的分析显示pirtobrutinib具有优势趋势（逆概率删失加权法：HR=0.89 [95% CI, 0.52-1.53]；两阶段加速失效时间法：HR=0.77 [95% CI, 0.45-1.26]）。

The overall safety profile for patients treated with pirtobrutinib in BRUIN CLL-321 was consistent with safety data from the Phase I/II BRUIN study, including adverse events of special interest. In the Phase III study, pirtobrutinib treatment was associated with fewer grade 3 or higher treatment-emergent adverse events (TEAEs) and fewer treatment discontinuations due to adverse events compared to IdelaR or BR.

在BRUIN CLL-321研究中，接受pirtobrutinib治疗的患者的整体安全性特征与I/II期BRUIN研究的安全性数据一致，包括特别关注的不良事件。在III期研究中，与IdelaR或BR相比，pirtobrutinib治疗相关的3级或更高级别的治疗相关紧急不良事件（TEAEs）较少，因不良事件导致的治疗中断也较少。

When adjusting for exposure, the incidence rate of TEAEs was overall lower in patients receiving pirtobrutinib compared to IdelaR or BR..

在调整暴露后，接受pirtobrutinib治疗的患者中TEAEs的发生率总体低于IdelaR或BR组。

'BRUIN CLL-321 is the only randomized CLL or SLL study ever conducted exclusively in the BTK-inhibitor pre-treated population, where there is significant need for new treatment options, and these data illustrate pirtobrutinib's ability to meaningfully delay disease progression and time to next treatment in this setting,' said David Hyman, M.D., chief medical officer, Lilly.

“BRUIN CLL-321 是唯一一项在既往接受过 BTK 抑制剂治疗的患者群体中进行的随机 CLL 或 SLL 研究，这一领域对新的治疗选择有显著需求，而这些数据表明 pirtobrutinib 能够在此背景下有效延缓疾病进展并推迟下一次治疗的时间，”礼来公司首席医学官 David Hyman 医学博士表示。

'This is the first in our suite of randomized Phase III trials for pirtobrutinib to readout and we look forward to continuing to build the body of evidence supporting the role of pirtobrutinib in advancing care for people with B-cell malignancies.'.

“这是pirtobrutinib的首项随机III期试验结果，我们期待继续积累证据，支持pirtobrutinib在改善B细胞恶性肿瘤患者治疗中的作用。”

Condition:

条件：

CLL/SLL

慢性淋巴细胞白血病/小淋巴细胞淋巴瘤

Type:

类型：

drug

药物