INDIANAPOLIS, Dec. 11, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced updated clinical data from the international Phase 1/2 BRUIN trial of pirtobrutinib, a non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor, in adult patients with a range of B-cell malignancies.

印第安纳波利斯，2023年12月11日/PRNewswire/--礼来公司（纽约证券交易所：LLY）今天宣布了国际1/2期布鲁替尼试验的最新临床数据，该试验是一种非共价（可逆）布鲁顿酪氨酸激酶（BTK）抑制剂，用于一系列B细胞恶性肿瘤的成年患者。

These data, which were presented in oral and poster presentations at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, continue to support the role of pirtobrutinib in the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL)..

这些数据在第65届美国血液学会（ASH）年会和博览会上以口头和海报形式呈现，继续支持pirtobrutinib在治疗慢性淋巴细胞白血病或小淋巴细胞淋巴瘤（CLL/SLL）和套细胞淋巴瘤（MCL）中的作用。。

'With longer follow-up, we continue to observe efficacy and tolerability data that support the potential utility of pirtobrutinib in CLL and B-cell lymphomas in the post-covalent BTK inhibitor setting,' said Matthew S. Davids, M.D., M.M.Sc., Dana-Farber Cancer Institute. 'These data demonstrate the ability of pirtobrutinib to potentially lengthen the time patients may benefit from inhibiting BTK, a key target in these diseases.

达纳-法伯癌症研究所（DanaFarber Cancer Institute）的马修·S·戴维斯（MatthewS.Davids）医学博士、医学硕士（M.M.Sc.）说：“随着随访时间的延长，我们继续观察到疗效和耐受性数据，这些数据支持吡妥布汀在共价BTK抑制剂后的CLL和B细胞淋巴瘤中的潜在效用。”这些数据表明，pirtobrutinib有可能延长患者从抑制BTK（这些疾病的关键靶标）中受益的时间。

It is also encouraging to see the promising initial data for pirtobrutinib combined with venetoclax, which has the possibility to allow for a time-limited regimen for patients with CLL.'.

同样令人鼓舞的是，pirtobrutinib联合venetoclax的有希望的初始数据，这有可能为CLL患者提供有时间限制的方案。

'Following the two FDA accelerated approvals for pirtobrutinib in 2023, we are excited to present these data at ASH, further building the body of evidence for this medicine in CLL, SLL, MCL, and other B-cell malignancies,' said David Hyman, M.D., chief medical officer, Lilly. 'These data support the potential role that pirtobrutinib, the first and only FDA-approved non-covalent BTK inhibitor, can play in extending the time patients may benefit from BTK inhibition therapy and provide additional efficacy data in patients previously treated with a covalent BTK inhibitor.

礼来首席医疗官大卫·海曼（DavidHyman）医学博士说：“在2023年FDA加速批准了两项吡妥布鲁替尼后，我们很高兴能在ASH上展示这些数据，进一步为这种药物在CLL、SLL、MCL和其他B细胞恶性肿瘤中的应用奠定了基础。”这些数据支持pirtobrutinib（第一个也是唯一一个FDA批准的非共价BTK抑制剂）在延长患者可能从BTK抑制治疗中受益的时间方面发挥的潜在作用，并为先前接受共价BTK抑制剂治疗的患者提供了额外的疗效数据。

We look forward to expanding our understanding of the broader potential clinical utility of pirtobrutinib as we continue to progress our series of randomized Phase 3 studies in CLL, SLL, and MCL.'.

随着我们继续在CLL，SLL和MCL中进行一系列随机3期研究，我们期待着扩大我们对pirtobrutinib更广泛的潜在临床应用的理解。

The labeling for pirtobrutinib contains warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, and embryo-fetal toxicity.

pirtobrutinib的标签包含感染，出血，血细胞减少，心律失常，第二原发性恶性肿瘤和胚胎-胎儿毒性的警告和预防措施。

Data from the BRUIN Phase 1/2 StudyThe BRUIN Phase 1/2 clinical trial is evaluating pirtobrutinib in patients previously treated for MCL, CLL/SLL, or other non-Hodgkin lymphomas (NHL). The efficacy data presented at ASH for CLL/SLL and MCL are based on independent review committee (IRC) assessment. All presentations of safety and efficacy data from the BRUIN Phase 1/2 trial utilized a cutoff date of May 5, 2023..

来自BRUIN 1/2期研究的数据BRUIN 1/2期临床试验正在评估先前接受过MCL，CLL/SLL或其他非霍奇金淋巴瘤（NHL）治疗的患者的吡妥布汀。ASH提供的CLL/SLL和MCL的疗效数据是基于独立审查委员会（IRC）的评估。BRUIN 1/2期试验的所有安全性和有效性数据的截止日期均为2023年5月5日。。

Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaAn oral presentation (Abstract #325) detailed updated, long-term follow-up data in patients with CLL/SLL. This data set consisted of 282 patients who had received a prior BTK inhibitor. Patients had received a median of four prior lines of therapy (range: 1-11).

慢性淋巴细胞白血病/小淋巴细胞淋巴瘤口腔表现（摘要#325）详细更新了CLL/SLL患者的长期随访数据。该数据集由282名先前接受过BTK抑制剂的患者组成。患者接受了四种治疗方案的中位数（范围：1-11）。

Efficacy results showed an overall response rate (ORR), including partial response with lymphocytosis (PR-L), of 81.6% (95% CI: 76.5, 85.9) for patients treated with pirtobrutinib. Response rates were consistent across all subgroups analyzed regardless of previous therapies, age, or mutation status.

疗效结果显示，吡妥布汀治疗患者的总有效率（ORR），包括淋巴细胞增多症（PR-L）的部分缓解率（ORR）为81.6%（95%CI:76.5,85.9）。无论以前的治疗方法，年龄或突变状态如何，所有分析的亚组的反应率都是一致的。

With a median follow-up of 27.5 months, median progression-free survival (PFS) was 19.4 months (95% CI: 16.6, 22.1). With a median follow-up of 29.3 months, median overall survival (OS) was not estimable..

中位随访27.5个月，中位无进展生存期（PFS）为19.4个月（95%CI:16.6，22.1）。中位随访29.3个月，中位总生存期（OS）无法估计。。

In patients treated with both a prior covalent BTK inhibitor and BCL-2 inhibitor (n=128, median of five prior lines of therapy, range: 1-11), pirtobrutinib demonstrated an ORR, including PR-L, of 79.7% (95% CI: 71.7, 86.3). With a median follow-up of 22.2 months, median PFS was 15.9 months (95% CI: 13.6, 17.5).

在既往接受共价BTK抑制剂和BCL-2抑制剂治疗的患者中（n=128，五种治疗方案的中位数，范围：1-11），吡妥布汀的ORR（包括PR-L）为79.7%（95%CI:71.7，86.3）。中位随访22.2个月，中位PFS为15.9个月（95%CI:13.6，17.5）。

With a median follow-up of 27.4 months, the median OS was not estimable..

中位随访时间为27.4个月，中位OS不可估计。。

In BCL-2-naïve patients (n=154, median of three prior lines of therapy, range: 1-9), pirtobrutinib demonstrated an ORR, including PR-L, of 83.1% (95% CI: 76.2, 88.7). With a median follow-up of 27.6 months, median PFS was 23.0 months (95% CI: 19.6, 28.4). With a median follow-up of 31.6 months, the median OS was not estimable..

在未接受BCL-2治疗的患者（n=154，三种治疗方案的中位数，范围：1-9）中，吡妥布汀的ORR（包括PR-L）为83.1%（95%CI:76.2，88.7）。中位随访27.6个月，中位PFS为23.0个月（95%CI:19.6，28.4）。中位随访31.6个月，中位OS无法估计。。

In the CLL/SLL safety cohort (n=282), the most frequent treatment-emergent adverse events (TEAEs) were fatigue (36.9%), neutropenia (34.4%), diarrhea (28.4%), cough (27.3%), and contusion (26.2%).

在CLL/SLL安全队列（n=282）中，最常见的治疗紧急不良事件（TEAE）是疲劳（36.9%），中性粒细胞减少（34.4%），腹泻（28.4%），咳嗽（27.3%）和挫伤（26.2%）。

A second oral presentation (Abstract #326) detailed updated analyses of genomic evolution and resistance during pirtobrutinib therapy in patients with relapsed covalent BTK inhibitor pre-treated CLL who subsequently developed disease progression on pirtobrutinib monotherapy (n=88). These data showed that although many patients harbored BTK mutations (C481 and non-C481) prior to initiation of pirtobrutinib therapy, these baseline genomic features did not predict response to pirtobrutinib.

第二次口头报告（摘要#326）详细分析了复发共价BTK抑制剂预处理的CLL患者在吡妥布汀治疗期间的基因组进化和耐药性，这些患者随后在吡妥布汀单药治疗中出现疾病进展（n=88）。这些数据表明，尽管许多患者在开始pirtobrutinib治疗之前携带BTK突变（C481和非C481），但这些基线基因组特征并不能预测对pirtobrutinib的反应。

Moreover, while many patients acquired mutations at progression (68%), fewer than half were in the BTK gene..

此外，尽管许多患者在进展中获得了突变（68%），但BTK基因的突变不到一半。。

A poster presentation (Abstract #3269) detailed updated data from the Phase 1b portion of the BRUIN trial, which investigated pirtobrutinib in combination with venetoclax with or without rituximab as a two-year fixed-duration therapy. This data set consisted of 25 patients, 17 of whom had received a prior BTK inhibitor.

海报介绍（摘要#3269）详细介绍了BRUIN试验1b期部分的最新数据，该试验研究了吡妥布汀联合venetoclax联合或不联合利妥昔单抗作为两年固定疗程的治疗方法。该数据集由25名患者组成，其中17名先前接受过BTK抑制剂。

Patients were enrolled into sequential cohorts, first in the pirtobrutinib plus venetoclax (PV) cohort (n=15) and then the PV plus rituximab (PVR) cohort (n=10). Efficacy results showed an ORR of 96% (95% CI: 79.6, 99.9), with 40% complete responses (PV, n=7; PVR, n=3) and 56% partial responses (PV, n=7; PVR, n=7) across the two arms.

患者被纳入连续队列，首先是pirtobrutinib加venetoclax（PV）队列（n=15），然后是PV加利妥昔单抗（PVR）队列（n=10）。疗效结果显示ORR为96%（95%CI:79.6,99.9），完全缓解率为40%（PV，n=7；PVR，n=3），部分缓解率为56%（PV，n=7；PVR，n=7）。

Undetectable minimal residual disease (uMRD) was achieved by 87.5% of patients (PV, n=12; PVR, n=9) at some time during the trial. Across the two arms, the PFS rate at 24 months was 79.5% (95% CI: 52.0, 92.3)..

在试验期间的某个时间，87.5%的患者（PV，n=12；PVR，n=9）实现了不可检测的最小残留病（uMRD）。在两臂中，24个月时的PFS率为79.5%（95%CI:52.0，92.3）。。

The primary endpoint was safety as assessed by TEAEs graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The safety profiles were generally similar among both combination treatment groups, and no dose limiting toxicities were observed. In the PV cohort, the most frequent treatment-related AEs were neutropenia (46.7%), nausea (46.7%), fatigue (33.3%), diarrhea (26.7%), and decreased platelet count (26.7%).

主要终点是根据不良事件通用术语标准（CTCAE）v5.0对TEAE评估的安全性。两个联合治疗组的安全性基本相似，没有观察到剂量限制性毒性。在PV队列中，最常见的治疗相关AE是中性粒细胞减少（46.7%），恶心（46.7%），疲劳（33.3%），腹泻（26.7%）和血小板计数下降（26.7%）。

In the PVR cohort, the most frequent treatment-related AEs were neutropenia (70.0%), diarrhea (60.0%), nausea (40.0%), infusion-related reactions (40.0%), and chills (30.0%). There were no apparent drug interactions between pirtobrutinib and venetoclax..

在PVR队列中，最常见的治疗相关AE是中性粒细胞减少症（70.0%），腹泻（60.0%），恶心（40.0%），输液相关反应（40.0%）和寒战（30.0%）。吡妥布汀和venetoclax之间没有明显的药物相互作用。。

These efficacy and safety data support the ongoing BRUIN CLL-322 Phase 3 trial evaluating two years of pirtobrutinib plus venetoclax and rituximab versus two years of venetoclax plus rituximab in previously treated CLL/SLL.

这些有效性和安全性数据支持正在进行的BRUIN CLL-322 3期临床试验，该试验评估了在先前治疗的CLL/SLL中两年的pirtobrutinib加venetoclax和rituximab与两年的venetoclax加rituximab。

Mantle Cell LymphomaAn oral presentation (Abstract #981) detailed updated efficacy results, including in high-risk subgroups. This data set consisted of 152 patients who had received a prior covalent BTK inhibitor. Patients had received a median of three prior lines of therapy (range: 1-9). Efficacy results showed an ORR of 49.3% (95% CI: 41.1, 57.6), including 15.8% complete responses (n=24) and 33.6% partial responses (n=51) for patients treated with pirtobrutinib.

套细胞淋巴瘤口服介绍（摘要#981）详细介绍了最新的疗效结果，包括高危亚组。该数据集由152名先前接受共价BTK抑制剂的患者组成。患者接受了三种治疗方案的中位数（范围：1-9）。疗效结果显示，吡妥布汀治疗患者的ORR为49.3%（95%CI:41.1,57.6），其中完全缓解率为15.8%（n=24），部分缓解率为33.6%（n=51）。

At a median follow-up of 14.7 months, the median duration of response (DOR) was 21.6 months (95% CI: 9.2, 27.2). Median PFS and OS were 5.6 months (95% CI: 5.3, 9.2) and 23.5 months (95% CI: 17.1, not estimable), respectively. Response rates were consistent across subgroups regardless of prior treatment or high-risk molecular features..

中位随访14.7个月，中位缓解期（DOR）为21.6个月（95%CI:9.2、27.2）。中位PFS和OS分别为5.6个月（95%CI:5.3、9.2）和23.5个月（95%CI:17.1，不可估计）。无论先前的治疗或高危分子特征如何，各亚组的反应率都是一致的。。

In the MCL safety cohort (n=166), the most frequent TEAEs were fatigue (31.9%), diarrhea (22.3%), and dyspnea (17.5%).

在MCL安全队列（n=166）中，最常见的TEAE是疲劳（31.9%），腹泻（22.3%）和呼吸困难（17.5%）。

Additionally, Lilly presented posters highlighting pirtobrutinib in relapsed or refractory follicular lymphoma (FL), relapsed or refractory marginal zone lymphoma (MZL), and Richter transformation (RT).

此外，礼来公司还发布了海报，重点介绍了复发或难治性滤泡性淋巴瘤（FL），复发或难治性边缘区淋巴瘤（MZL）和里氏转化（RT）中的吡妥布汀。

Loxo@Lilly is studying pirtobrutinib in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.

loxo@lilly正在多个3期研究中研究pirtobrutinib。有关试验的详细信息，请访问clinicaltrials.gov。

About the BRUIN Phase 1/2 TrialThe BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of pirtobrutinib in patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL).

关于BRUIN 1/2期试验BRUIN 1/2期临床试验是正在进行的第一项针对血液系统恶性肿瘤患者（包括慢性淋巴细胞白血病（CLL），小淋巴细胞淋巴瘤（SLL））和套细胞淋巴瘤（MCL）的吡妥布汀的人类，全球，多中心评估。

The BRUIN trial includes one of the largest prospective cohorts of BTK inhibitor pre-treated CLL/SLL patients ever studied..

BRUIN试验包括BTK抑制剂预处理的CLL/SLL患者有史以来最大的前瞻性队列之一。。

The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by overall response rate (ORR) for monotherapy.

该试验包括1期剂量递增阶段，1b期联合组和2期剂量扩展阶段。第一阶段研究的主要终点是最大耐受剂量（MTD）/推荐的第二阶段剂量（RP2D）。次要终点包括安全性，药代动力学（PK）和通过单药治疗的总有效率（ORR）测量的初步疗效。

The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an independent review committee (IRC). Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and PK..

1b期研究的主要终点是药物组合的安全性。次要终点是PK和ORR测量的药物组合的初步疗效。第二阶段研究的主要终点是由独立审查委员会（IRC）确定的ORR。次要终点包括研究者确定的ORR，最佳总体反应（BOR），反应持续时间（DOR），无进展生存期（PFS），总生存期（OS），安全性和PK。。

About PirtobrutinibPirtobrutinib is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation, and survival of normal white blood cells, known as B-cells, and malignant B-cells.

关于PirtobrutinibPirtobrutinib是一种高选择性（对BTK的选择性是临床前研究中测试的其他激酶的98%的300倍），BTK酶的非共价（可逆）抑制剂。BTK在B细胞抗原受体信号传导途径中起关键作用，这是正常白细胞（称为B细胞）发育，活化和存活所必需的，和恶性B细胞。

BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).2,3 Pirtobrutinib was developed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, and preserve activity in the presence of the C481 acquired resistance mutations..

BTK是在许多B细胞白血病和淋巴瘤（包括套细胞淋巴瘤（MCL）和慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL））中发现的经过验证的分子靶标。2,3 Pirtobrutinib被开发用于可逆地结合BTK，无论BTK周转率如何，都能提供始终如一的高靶标覆盖率，并在存在C481获得性耐药突变的情况下保持活性。。

Pirtobrutinib was approved under the FDA's Accelerated Approval pathway as Jaypirca® (pirtobrutinib) on January 27, 2023, to treat adult patients with relapsed or refractory MCL after at least two lines of systemic therapy, including a BTK inhibitor, and on December 1, 2023, to treat adult patients with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

2023年1月27日，Pirtobrutinib在FDA加速批准途径下被批准为Jaypirca®（Pirtobrutinib），用于治疗至少两种全身治疗（包括BTK抑制剂）后复发或难治性MCL的成年患者，并于2023年12月1日批准用于治疗至少接受过两种治疗方案的CLL/SLL成年患者，包括BTK抑制剂和BCL-2抑制剂。

These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial..

这些适应症是根据响应率加速批准的。这些适应症的持续批准可能取决于验证性试验中临床益处的验证和描述。。

INDICATIONS FOR JAYPIRCAJaypirca is a kinase inhibitor indicated for the treatment of

JAYPIRCAJaypirca的适应症是一种激酶抑制剂，用于治疗

Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.

至少两种全身治疗（包括BTK抑制剂）后复发或难治性套细胞淋巴瘤（MCL）的成年患者。

Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

患有慢性淋巴细胞白血病或小淋巴细胞淋巴瘤（CLL/SLL）的成年患者，他们至少接受过两种治疗方案，包括BTK抑制剂和BCL-2抑制剂。

These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

这些适应症是根据响应率加速批准的。继续批准这些适应症可能取决于验证性试验中临床益处的验证和描述。

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA® (pirtobrutinib)

JAYPIRCA®（pirtobrutinib）的重要安全信息

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred in 4.4%.

感染：Jaypirca治疗的患者发生致命和严重感染（包括细菌，病毒，真菌）和机会性感染。在一项临床试验中，24%的血液系统恶性肿瘤患者发生≥3级感染，最常见的是肺炎（14%）；致命感染发生率为4.4%。

Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections.

发生败血症（6%）和发热性中性粒细胞减少症（4%）。在CLL/SLL患者中，发生≥3级感染（32%），致命感染发生率为8%。机会性感染包括肺孢子虫肺炎和真菌感染。考虑对感染风险增加（包括机会性感染）的患者进行预防，包括接种疫苗和抗菌药物预防。

Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca..

监测患者的体征和症状，及时评估并进行适当治疗。根据严重程度，减少剂量，暂时停止或永久停止Jaypirca。。

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred in 17%.

出血：Jaypirca发生致命和严重的出血。3%的患者发生大出血（3级以上出血或任何中枢神经系统出血），包括胃肠道出血；发生致命性出血（0.3%）。除瘀伤和瘀斑外，任何级别的出血发生率均为17%。

Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

服用Jaypirca（0.7%）和不服用（2.3%）抗血栓药物的患者发生大出血。考虑与Jaypirca共同服用抗血栓药物的风险/益处。监测患者是否有出血迹象。根据严重程度，减少剂量，暂时停止或永久停止Jaypirca。

Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk..

根据手术类型和出血风险，考虑手术前后3-7天停用Jaypirca的益处/风险。。

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed.

血细胞减少症：Jaypirca可引起血细胞减少症，包括中性粒细胞减少症，血小板减少症和贫血。在一项临床试验中，接受Jaypirca治疗的患者出现了3或4级血细胞减少症，包括中性粒细胞减少（26%），血小板减少（12%）和血红蛋白减少（12%）。4级中性粒细胞减少（14%），4级血小板减少（6%）。

Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca..

在治疗期间定期监测全血细胞计数。根据严重程度，减少剂量，暂时停止或永久停止Jaypirca。。

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%).

心律失常：接受Jaypirca治疗的患者发生心律失常。在一项针对血液系统恶性肿瘤患者的临床试验中，Jaypirca治疗的患者中有3.2%报告有房颤或扑动，3或4级房颤或扑动的发生率为1.5%。其他严重心律失常如室上性心动过速和心脏骤停发生（0.5%）。

Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca..

患有高血压或既往心律失常等心脏危险因素的患者风险可能会增加。监测心律失常的体征和症状（例如心悸，头晕，晕厥，呼吸困难）并进行适当管理。根据严重程度，减少剂量，暂时停止或永久停止Jaypirca。。

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma.

第二原发性恶性肿瘤：在接受Jaypirca治疗的患者中，有9%发生了第二原发性恶性肿瘤，包括非皮肤癌。最常见的恶性肿瘤是非黑色素瘤皮肤癌（4.6%）。其他第二原发性恶性肿瘤包括实体瘤（包括泌尿生殖道和乳腺癌）和黑色素瘤。

Advise patients to use sun protection and monitor for development of second primary malignancies..

建议患者使用防晒霜并监测第二原发性恶性肿瘤的发展。。

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats during organogenesis caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose.

胚胎-胎儿毒性：Jaypirca可对孕妇造成胎儿伤害。在器官发生过程中向怀孕大鼠施用pirtobrutinib会导致胚胎-胎儿毒性，包括胚胎-胎儿死亡率和母体暴露时的畸形（AUC），约为推荐的200 mg/天剂量的3倍。

Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose..

建议有潜在胎儿风险的孕妇和有生殖潜力的女性在治疗期间和最后一剂后一周内使用有效的避孕措施。。

Adverse Reactions (ARs) in Patients Who Received JaypircaThe most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%)..

接受jaypirca治疗的患者的不良反应（AR）在血液系统恶性肿瘤患者（n=593）的BRUIN合并安全人群中，最常见（≥20%）的AR是中性粒细胞计数减少（46%），血红蛋白减少（39%），疲劳（32%），淋巴细胞计数减少（31%），肌肉骨骼疼痛（30%），血小板计数减少（29%），腹泻（24%），COVID-19（22%），瘀伤（21%），咳嗽（20%）。。

Mantle Cell LymphomaSerious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients)..

38%的患者发生套细胞淋巴瘤性ARs。在≥2%的患者中发生的严重ARs是肺炎（14%），新型冠状病毒肺炎（4.7%），肌肉骨骼疼痛（3.9%），出血（2.3%），胸腔积液（2.3%）和败血症（2.3%）。在最后一次Jaypirca剂量的28天内，7%的患者发生致命的ARs，最常见的原因是感染（4.7%），包括新型冠状病毒肺炎（COVID-19）（占所有患者的3.1%）。。

Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia..

剂量调整和停药：ARs导致剂量减少4.7%，治疗中断32%，9%的患者永久停用Jaypirca。导致>5%患者剂量改变的ARs包括肺炎和中性粒细胞减少症。ARs导致超过1%的患者永久停药，包括肺炎。。

ARs (all Grades %; Grade 3-4 %) in ≥10% of Patients: fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -), peripheral neuropathy (14; 0.8), cough (14; -), rash (14; -), fever (13; -), constipation (13; -), arthritis/arthralgia (12; 0.8), hemorrhage (11; 3.1), abdominal pain (11; 0.8), nausea (11; -), upper respiratory tract infections (10; 0.8), dizziness (10; -)..

≥10%患者的ARs（所有等级；3-4%）：疲劳（29；1.6），肌肉骨骼疼痛（27；3.9），腹泻（19；-），水肿（18；0.8），呼吸困难（17；2.3），肺炎（16；14），瘀伤（16；-），周围神经病变（14；0.8），咳嗽（14；-），皮疹（14；-），发烧（13；-），便秘（13；-），关节炎/关节痛（12；0.8），出血（11；3.1），腹痛（11；0.8），恶心（11；-），上呼吸道感染（10；0.8），头晕（10；-）。。

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8).

在≥10%的患者中，从基线开始恶化的实验室异常（所有级别；3级或4级）：血红蛋白降低（42；9），血小板计数降低（39；14），中性粒细胞计数降低（36；16），淋巴细胞计数降低（32；15），肌酐升高（30；1.6），钙降低（19；1.6），AST升高（17；1.6），钾降低（13；1.6），钠降低（13；-），脂肪酶增加（12；4.4），碱性磷酸酶增加（11；-），ALT增加（11；1.6），钾增加（11；0.8）。

Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6). .

>5%的患者的4级实验室异常包括中性粒细胞减少（10），血小板减少（7），淋巴细胞减少（6）。。

Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaSerious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%)..

56%的患者发生慢性淋巴细胞白血病/小淋巴细胞淋巴瘤性ARs。≥5%的患者发生严重的ARs是肺炎（18%），新型冠状病毒肺炎（9%），败血症（7%）和发热性中性粒细胞减少症（7%）。11%的患者在最后一次服用Jaypirca后28天内发生致命性ARs，最常见的原因是感染（10%），包括败血症（5%）和新型冠状病毒肺炎（2.7%）。。

Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis..

剂量调整和停药：ARs导致剂量减少3.6%，治疗中断42%，9%的患者永久停用Jaypirca。导致剂量减少>1%的ARs包括中性粒细胞减少症；>5%的患者的治疗中断包括肺炎，中性粒细胞减少症，发热性中性粒细胞减少症和新型冠状病毒肺炎；超过1%的患者永久停药包括第二原发性恶性肿瘤，新型冠状病毒肺炎和败血症。。

ARs (all Grades %; Grade 3-4 %) in ≥10% of Patients: fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9), arthritis/arthralgia (19; 1.8), rash (19; 0.9), peripheral neuropathy (16; 3.6), dizziness (15; -), fall (14; 0.9), constipation (14; -), insomnia (14; -), upper respiratory tract infections (13; 2.7), second primary malignancy (13; 2.7), renal insufficiency (12; 6), hypertension (12; 5), neurological changes (12; 2.7), mucositis (12; 0.9), decreased appetite (12; -), respiratory tract infection (11; 1.8), supraventricular tachycardia (10; 5)..

≥10%患者的ARs（所有等级；3-4%）：疲劳（36；2.7），瘀伤（36；-），咳嗽（33；-），肌肉骨骼疼痛（32；0.9），新型冠状病毒肺炎（28；7），肺炎（27；16），腹泻（26；-），腹痛（25；2.7），呼吸困难（22；2.7），出血（22；2.7），水肿（21；-），恶心（21；-），发热（20；2.7），头痛（20；0.9），关节炎/关节痛（19；1.8），皮疹（19；0.9），周围神经病变（16；3.6），头晕（15；-），跌倒（14；0.9），便秘（14；-），失眠（14；-），上呼吸道感染（13；2.7），第二原发性恶性肿瘤（13；2.7），肾功能不全（12；6），高血压（12；5），神经系统改变（12；2.7），粘膜炎（12；0.9），食欲下降（12；-），呼吸道感染（11；1.8），室上性心动过速（10；5）。。

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -).

在≥20%的患者中，从基线开始恶化的实验室异常（所有等级；3级或4级）：中性粒细胞计数减少（63；45），血红蛋白减少（48；19），钙减少（40；2.8），血小板计数减少（30；15），钠减少（30；-），淋巴细胞计数减少（23；8），ALT增加（23；2.8），AST增加（23；1.9），肌酐增加（23；-），脂肪酶增加（21；7），碱性磷酸酶增加（21；-）。

Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23). .

>5%的患者的4级实验室异常包括中性粒细胞减少（23）。。

Drug InteractionsStrong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.

药物相互作用强CYP3A抑制剂：与Jaypirca同时使用会增加pirtobrutinib全身暴露，这可能会增加Jaypirca ARs的风险。避免将强CYP3A抑制剂与Jaypirca一起使用。如果不可避免地同时使用，请根据批准的标签减少Jaypirca的剂量。

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling..

强或中度CYP3A诱导剂：与Jaypirca同时使用可减少吡妥布汀全身暴露，这可能会降低Jaypirca的疗效。避免将Jaypirca与强或中度CYP3A诱导剂同时使用。如果不可避免地与中度CYP3A诱导剂同时使用，请根据批准的标签增加Jaypirca的剂量。。

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling..

敏感的CYP2C8，CYP2C19，CYP3A，P-gp或BCRP底物：与Jaypirca同时使用会增加其血浆浓度，这可能会增加对最小浓度变化敏感的药物与这些底物相关的不良反应风险。遵循这些敏感底物在其批准标签中的建议。。

Use in Special Populations Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown.

在特殊人群怀孕和哺乳期使用：由于Jaypirca可能会对胎儿造成伤害，因此在开始使用Jaypirca之前，请验证具有生殖潜力的女性的妊娠状况，并建议在治疗期间和最后一次服用后一周内使用有效的避孕措施。人乳中是否存在pirtobrutinib尚不清楚。

Advise women not to breastfeed while taking Jaypirca and for one week after last dose..

建议女性服用Jaypirca时以及服用最后一剂后一周内不要母乳喂养。。

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

老年使用：在血液系统恶性肿瘤患者的汇总安全人群中，与65岁以下的患者相比，≥65岁的患者经历≥3级ARs和严重ARs的发生率更高。

Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.

肾功能不全：严重的肾功能不全会增加pirtobrutinib的暴露。根据批准的标签，减少严重肾功能不全患者的Jaypirca剂量。

PT HCP ISI COMBO DEC2023

PT-HCP-ISI组合，2023年12月

Please see Prescribing Information and Patient Information for Jaypirca.

请参阅Jaypirca的处方信息和患者信息。

About Lilly

关于莉莉

Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases.

礼来将关怀与发现结合起来，创造出让全世界人民生活得更好的药物。近150年来，我们一直在开创改变生活的发现，今天，我们的药物帮助了全球5100多万人。利用生物技术、化学和遗传医学的力量，我们的科学家正在迫切推进新的发现，以解决世界上一些最重大的健康挑战，重新定义糖尿病护理，治疗肥胖并减少其最具破坏性的长期影响，推进对抗阿尔茨海默氏病的斗争，为一些最令人衰弱的免疫系统疾病提供解决方案，并将最难治疗的癌症转化为可控制的疾病。

With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, and LinkedIn.

在迈向更健康世界的每一步中，我们都有一个动机：让数百万人的生活变得更好。这包括提供反映我们世界多样性的创新临床试验，并努力确保我们的药物可获得且负担得起。要了解更多信息，请访问Lilly.com和Lilly.com/newsroom，或在Facebook、Instagram和LinkedIn上关注我们。

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Jaypirca® is a registered trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.

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Lilly Cautionary Statement Regarding Forward-Looking Statements

关于前瞻性声明的礼来警示声明

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about pirtobrutinib as a treatment for adult patients with mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor, as a treatment for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor, and a potential treatment for follicular lymphoma (FL), relapsed or refractory marginal zone lymphoma (MZL), and Richter transformation (RT) and reflects Lilly's current beliefs and expectations.

本新闻稿包含关于pirtobrutinib的前瞻性声明（该术语在1995年《私人证券诉讼改革法案》中有定义），该药物用于治疗至少两种全身治疗（包括BTK抑制剂）后的成人套细胞淋巴瘤（MCL），作为一种治疗慢性淋巴细胞白血病或小淋巴细胞淋巴瘤（CLL/SLL）的成年患者的方法，这些患者至少接受过两种治疗方案，包括BTK抑制剂和BCL-2抑制剂，以及滤泡性淋巴瘤（FL），复发或难治性边缘区淋巴瘤（MZL）的潜在治疗方法，和里氏变换（RT），反映了礼来目前的信念和期望。

However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, or that pirtobrutinib will receive additional regulatory approvals.

然而，与任何药品一样，药物研究，开发和商业化过程中存在重大风险和不确定性。除其他外，不能保证计划或正在进行的研究将按计划完成，未来的研究结果将与迄今为止的研究结果一致，或者pirtobrutinib将获得额外的监管批准。

For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release..

有关这些以及其他可能导致实际结果与礼来预期不同的风险和不确定性的进一步讨论，请参阅礼来向美国证券交易委员会提交的表格10-K和表格10-Q。除法律要求外，礼来没有义务更新前瞻性声明以反映本发布日期后的事件。。

Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. doi:10.1016/S0140-6736(21)00224-5

Mato AR，Shah NN，Jurczak W等。Pirtobrutinib治疗复发或难治性B细胞恶性肿瘤（BRUIN）：1/2期研究。柳叶刀。2021年；397（10277）：892-901。doi:10.1016/S0140-6736（21）00224-5

Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. Published 2020 Jun 17. doi:10.1186/s13045-020-00914-1

Hanel W，Epperla N.套细胞淋巴瘤的新兴疗法。J Hematol Oncol。2020年；13（1）：79。2020年6月17日出版。内政部：10.1186/s13045-020-00914-1

Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021;14(1):40. Published 2021 Mar 6. doi:10.1186/s13045-021-01049-7

Gu D，Tang H，Wu J，Li J，Miao Y.在B细胞恶性肿瘤中使用非共价抑制剂靶向布鲁顿酪氨酸激酶。J Hematol Oncol。2021年；14（1）：40。2021年3月6日出版。内政部：10.1186/s13045-021-01049-7

Refer to:

请参阅：

Kyle Owens; [email protected]; (332) 259-3932 – media

凯尔·欧文斯；[受电子邮件保护]；（332）259-3932–媒体

Joe Fletcher; [email protected]; (317) 296-2884 – investors

乔·弗莱彻；[受电子邮件保护]；（317）296-2884–投资者

SOURCE Eli Lilly and Company

来源：礼来公司