New longer-term data from the MARIPOSA study confirm superior outcomes of chemotherapy-free RYBREVANT® plus LAZCLUZE™ regimen compared to osimertinib monotherapy as first-line therapy

来自MARIPOSA研究的新的长期数据证实，与作为一线治疗的osimertinib单一疗法相比，无化疗的RYBREVANT®加LAZCLUZE™方案具有更好的疗效

Results from an interim analysis featured in late-breaker oral presentation at WCLC

在WCLC的晚期断路器口头演示中进行的中期分析结果

SAN DIEGO, Sept. 8, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced longer follow-up data from the landmark Phase 3 MARIPOSA study which showed first-line treatment with RYBREVANT® (amivantamab-vmjw) combined with LAZCLUZE™ (lazertinib) provided consistent benefit across long-term outcomes compared to osimertinib monotherapy in adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations.

圣地亚哥，2024年9月8日/新闻通讯社/--强生（纽约证券交易所：JNJ）今天宣布了具有里程碑意义的3期MARIPOSA研究的更长时间的随访数据，该研究显示RYBREVANT®（amivantamab vmjw）联合LAZCLUZE™（lazertinib）的一线治疗与osimertinib单药治疗成人晚期非小细胞肺癌（NSCLC）患者表皮生长因子受体（EGFR）外显子19缺失（ex19del）或L858R替代突变相比，长期疗效一致。

The data show a strong and improving overall survival (OS) trend favoring RYBREVANT® plus LAZCLUZE™ at approximately three years of follow-up. These results were presented in a late-breaking oral presentation at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC) (Abstract #1146).1.

数据显示，在大约三年的随访中，RYBREVANT®加LAZCLUZE™的总体生存率（OS）呈上升趋势。这些结果在国际肺癌研究协会（IASLC）2024年世界肺癌会议（WCLC）（摘要#1146）的最新口头报告中发表。

At three years (a median follow-up of 31.1 months), 61 percent of patients receiving RYBREVANT® plus LACLUZE™ were alive compared to 53 percent of those treated with osimertinib based on an analysis performed at the request of a health authority (Median OS not estimable vs 37.3 months; hazard ratio [HR], 0.77; [95 percent confidence interval [CI], 0.61-0.96]; nominal P=0.019).

在三年（中位随访31.1个月）时，根据卫生部门的要求进行的分析，接受RYBREVANT®plus-LACLUZE™治疗的患者中有61%存活，而接受osimertinib治疗的患者中有53%存活（中位OS不可估计vs 37.3个月；风险比[HR]，0.77；[95%置信区间[CI]，0.61-0.96]；标称P=0.019）。

Overall survival will continue to be assessed with longer term follow-up as a key secondary endpoint. The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR).1.

总体生存率将继续通过长期随访作为关键的次要终点进行评估。主要疗效指标是通过盲法独立中央评估（BICR）评估的无进展生存期（PFS）。

'By combining the multi-targeted mechanism of RYBREVANT with LAZCLUZE, a central nervous system-penetrant third-generation tyrosine kinase inhibitor, we are advancing a chemotherapy-free regimen for the first-line treatment of patients with EGFR-mutant NSCLC. This approach blocks EGFR and MET pathways and leverages the immune system, offering patients an opportunity for prolonged benefits,' said Shirish M.

“通过将RYBREVANT的多靶点机制与中枢神经系统渗透性第三代酪氨酸激酶抑制剂LAZCLUZE相结合，我们正在推进一种无化疗方案，用于EGFR突变NSCLC患者的一线治疗。ShirishM。

Gadgeel, M.D., Chief of Division of Hematology and Oncology, Associate Director at Henry Ford Cancer Institute and presenting author.* 'Even more encouraging is the marked improvement in the hazard ratio and the ongoing separation of survival curves, showing an eight percent improvement at three years for RYBREVANT plus LAZCLUZE compared to osimertinib.

医学博士Gadgeel，血液学和肿瘤学系主任，亨利福特癌症研究所副所长兼报告作者。*更令人鼓舞的是，风险比的显着改善和生存曲线的持续分离，显示RYBREVANT plus LAZCLUZE与osimertinib相比，三年后改善了8%。

This supports the long-term benefit of the combination as a first-line treatment option in this setting.'.

这支持了在这种情况下作为一线治疗选择的组合的长期益处。”。

Results further showed RYBREVANT® plus LAZCLUZE™ demonstrated a trend toward improved central nervous system disease control compared to osimertinib at three years (HR, 0.82; [95 percent CI, 0.62-1.09]; nominal P=0.165). At the three-year landmark, intracranial PFS was double for RYBREVANT® plus LAZCLUZE™ versus osimertinib (38 percent vs 18 percent, respectively).

结果进一步显示，与osimertinib相比，RYBREVANT®plus LAZCLUZE™在三年时表现出改善中枢神经系统疾病控制的趋势（HR，0.82；[95%可信区间，0.62-1.09]；标称P=0.165）。。

More patients remained on treatment at three years with the RYBREVANT® combination compared to osimertinib (40 percent vs 29 percent, respectively; HR, 0.80; [95 percent CI, 0.68-0.96]; nominal P=0.014). Additionally, more patients receiving RYBREVANT® and LAZCLUZE™ at the three-year follow-up had not started a subsequent therapy versus osimertinib (45 percent vs 32 percent, respectively; HR, 0.77; [95 percent CI, 0.65-0.93]; nominal P=0.005).

与osimertinib相比，更多的患者在使用RYBREVANT®联合治疗三年后仍在接受治疗（分别为40%和29%；HR为0.80；[95%CI为0.68-0.96]；标称P=0.014）。。

Progression-free survival after first subsequent therapy was 57 percent for the RYBREVANT® combination compared to 49 percent for osimertinib (HR, 0.73; [95 percent CI, 0.59-0.91]; nominal P=0.004).1.

RYBREVANT®联合治疗后首次随访的无进展生存率为57%，而osimertinib为49%（HR，0.73；[95%CI，0.59-0.91]；标称P=0.004）。

'Promising results like these presented at WCLC reinforce our mission to improve the lives of patients diagnosed with lung cancer,' said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. 'We are encouraged by the favorable overall survival trend observed with RYBREVANT plus LAZCLUZE and are eager to see how these data evolve as we continue to follow patients over time.' .

强生创新医学公司（Johnson&Johnson Innovative Medicine）肺癌疾病领域大本营负责人、副总裁约书亚·鲍姆（JoshuaBauml）医学博士（M.D.）说，在WCLC上展示的这些令人鼓舞的结果强化了我们改善被诊断患有肺癌的患者生活的使命我们对RYBREVANT plus LAZCLUZE观察到的有利的总体生存趋势感到鼓舞，并渴望看到随着时间的推移，随着我们继续跟踪患者，这些数据是如何演变的。”。

As previously reported in the MARIPOSA study, the safety profile was consistent with the safety profiles of the individual treatments. The rate of discontinuation of all study treatments due to treatment-related adverse events for RYBREVANT® plus LAZCLUZE™ was 10 percent. The rate of interstitial lung disease (including pneumonitis) was less than three percent in both arms.2.

正如先前在MARIPOSA研究中报道的那样，安全性与个体治疗的安全性一致。由于RYBREVANT®plus LAZCLUZE™的治疗相关不良事件，所有研究治疗的中断率为10%。两组间质性肺病（包括肺炎）的发生率均低于3%。

In August 2024, RYBREVANT® combined with LAZCLUZE™ was approved following a Priority Review by the U.S. Food and Drug Administration as a first-line therapy for patients with EGFR-mutated NSCLC based on the favorable efficacy and safety profile demonstrated in this study.

2024年8月，根据本研究显示的良好疗效和安全性，RYBREVANT®联合LAZCLUZE™在美国食品和药物管理局的优先审查后被批准作为EGFR突变NSCLC患者的一线治疗。

About the MARIPOSA Study

关于MARIPOSA研究

MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT® in combination with LAZCLUZE™ versus osimertinib and versus LAZCLUZE™ alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.

MARIPOSA（NCT04487080）招募了1074名患者，是一项随机的3期研究，评估RYBREVANT®联合LAZCLUZE™与osimertinib和单独使用LAZCLUZE™一线治疗EGFR ex19del或L858R替代突变的局部晚期或转移性NSCLC患者。

The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by BICR. Secondary endpoints include OS, overall response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS.3.

该研究的主要终点是BICR评估的PFS（使用RECIST v1.1指南）。次要终点包括OS，总有效率（ORR），反应持续时间（DOR），第二无进展生存期（PFS2）和颅内PFS。

About RYBREVANT®

关于[UNK]RYBREVANT®

RYBREVANT® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe, and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.4.

RYBREVANT®（amivantamab vmjw）是一种靶向EGFR并具有免疫细胞导向活性的全人双特异性抗体，已在美国获得批准。S、 ，欧洲和世界其他市场作为单一疗法，用于治疗具有EGFR外显子20插入突变的局部晚期或转移性NSCLC的成年患者，如FDA批准的测试所检测到的，其疾病在铂类化疗时或之后进展。

RYBREVANT® is approved in the U.S., Europe and in markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test..

RYBREVANT®在美国，欧洲和世界各地的市场被批准与化疗（卡铂和培美曲塞）联合用于一线治疗具有EGFR外显子20插入突变的局部晚期或转移性NSCLC的成年患者，这是通过FDA批准的测试检测到的。。

RYBREVANT® is approved in the U.S. in combination with LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. A marketing authorization application (MAA) and type II extension of indication application were submitted to the European Medicines Agency (EMA) seeking approval of LAZCLUZE™ in combination with RYBREVANT® based on the MARIPOSA study. .

RYBREVANT®在美国被批准与LAZCLUZE™（lazertinib）联合用于一线治疗具有EGFR外显子19缺失或L858R替代突变的局部晚期或转移性NSCLC的成年患者，这是通过FDA批准的测试检测到的。根据MARIPOSA研究，向欧洲药品管理局（EMA）提交了上市授权申请（MAA）和II型适应症扩展申请，寻求批准LAZCLUZE™与RYBREVANT®联合使用。。

In November 2023, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA for RYBREVANT® in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. This indication was approved in Europe in August 2024..

。该适应症于2024年8月在欧洲获得批准。。

In June 2024, Johnson & Johnson submitted a BLA to the U.S. FDA for the subcutaneous formulation of RYBREVANT® in combination with LAZCLUZE™ for all currently approved or submitted indications of intravenous (IV) RYBREVANT® in certain patients with NSCLC. A submission for the extension of the RYBREVANT® marketing authorization (line extension) was also submitted to the EMA seeking approval for this indication..

2024年6月，强生公司向美国食品和药物管理局提交了一份BLA，用于RYBREVANT®与LAZCLUZE™的皮下制剂，用于某些NSCLC患者目前批准或提交的所有静脉注射（IV）RYBREVANT®适应症。RYBREVANT®营销授权扩展（线路扩展）的提交文件也已提交给EMA，以寻求对该指示的批准。。

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:

针对NSCLC的NCCN肿瘤学临床实践指南（NCCN Guidelines®）更喜欢基于下一代测序的策略，而不是基于聚合酶链反应的方法来检测EGFR外显子20插入变体。NCCN指南包括：

Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a preferred (Category 1 preferred recommendation) subsequent therapy for patients with locally advanced or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with Osimertinib.5 †‡Amivantamab-vmjw (RYBREVANT®) plus carboplatin and pemetrexed as a preferred (Category 1 preferred recommendation) first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.5 †‡Amivantamab-vmjw (RYBREVANT®) as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.5 †‡In addition to the Phase 3 MARIPOSA study, RYBREVANT® is being studied in multiple clinical trials in NSCLC, including:.

对于在铂类化疗（有或没有免疫治疗）或铂类化疗后进展且EGFR外显子20插入突变阳性的NSCLC患者。5†‡除了3期MARIPOSA研究外，RYBREVANT®正在NSCLC的多项临床试验中进行研究，包括：。

The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT® (with or without LAZCLUZE™) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib.6The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT® in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.7The Phase 3 PALOMA-3 (NCT05388669) study assessing LAZCLUZE™ with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.8The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.9The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab subcutaneous delivery.10The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT® in patients with advanced NSCLC.11The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT® in combination with LAZCLUZE™ and LAZCLUZE™ as a monotherapy in patients with advanced NSCLC with EGFR.12The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT® and capmatinib combination therapy in locally advanced or metastatic NSCLC.13The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.14The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of f.

3期MARIPOSA-2（NCT04988295）研究评估了局部晚期或转移性EGFR ex19del或L858R替代NSCLC患者在osimertinib或osimertinib后疾病进展后RYBREVANT®（有或没有LAZCLUZE™）和卡铂-培美曲塞与卡铂-培美曲塞单独治疗的疗效。6 3期PAPILLON（NCT04538664）研究评估了RYBREVANT®联合卡铂-培美曲塞与单独化疗在一线治疗EGFR外显子20插入突变的晚期或转移性NSCLC患者中的疗效。-3（NCT05388669）研究评估LAZCLUZE™与皮下阿米万塔单抗相比，静脉注射阿米万塔单抗治疗EGFR突变的晚期或转移性NSCLC患者。8 2期PALOMA-2（NCT05498428）研究评估皮下阿米万塔单抗治疗晚期或转移性实体瘤患者，包括EGFR突变的NSCLC。9 1期PALOMA（NCT04606381）研究基于安全性和药代动力学评估皮下注射阿米万塔单抗的可行性，并确定阿米万塔单抗皮下给药的剂量，剂量方案和配方。10评估晚期非小细胞肺癌患者RYBREVANT®的1期蛹（NCT02609776）研究。11 1/1b期蛹-2（NCT04077463）研究评估RYBREVANT®联合LAZCLUZE™和LAZCLUZE™作为EGFR晚期非小细胞肺癌患者的单一疗法。12评估RYBREVANT®和卡马替尼联合治疗的1/2期METalmark（NCT05488314）研究局部晚期或转移性非小细胞肺癌的治疗[13]。1/2期PolyDamas（NCT05908734）研究评估了RYBREVANT®和cetrelimab联合治疗局部晚期或转移性非小细胞肺癌[14]。2期SKIPPirr研究（NCT05663866）探讨了如何降低f的发生率和/或严重程度。

About LAZCLUZE™

关于Lazcluze™

In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE™ (marketed as LACLAZA in Korea). LAZCLUZE™ is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR.

2018年，Janssen Biotech，Inc.与Yuhan Corporation签订了LAZCLUZE™开发许可证和合作协议（在韩国以LACLAZA的名义销售）。LAZCLUZE™是一种口服的第三代脑渗透性EGFR TKI，可靶向T790M突变和激活EGFR突变，同时保留野生型EGFR。

An analysis of the efficacy and safety of LAZCLUZE™ from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023. .

。

About Non-Small Cell Lung Cancer

关于非小细胞肺癌

Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.19,20 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.21 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.22 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.21,22,23,24,25,26 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.27 The five- year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.28,29 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.30 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.31.

在世界范围内，肺癌是最常见的癌症之一，非小细胞肺癌占所有肺癌病例的80%至85%.19,20非小细胞肺癌的主要亚型是腺癌，鳞状细胞癌和大细胞癌.21非小细胞肺癌中最常见的驱动突变是EGFR的改变，EGFR是一种控制细胞生长和分裂的受体酪氨酸激酶.22 EGFR突变存在于10%至15%的西方非小细胞肺癌腺癌组织学患者中，发生在40%至50%的亚洲患者中.21,22,23,24,25,26 EGFR ex19del或EGFR L858R突变是最常见的EGFR突变.27五年生存率对于所有接受EGFR酪氨酸激酶抑制剂（TKIs）治疗的晚期NSCLC和EGFR突变患者，其比例不到20%。28,29 EGFR外显子20插入突变是第三大最常见的激活EGFR突变。30 EGFR外显子20插入突变患者在一线环境中的实际五年总生存率（OS）为8%，这比EGFR ex19del或L858R突变患者更糟糕，他们的实际五年OS为19%。

IMPORTANT SAFETY INFORMATION4,32

重要安全信息4,32

WARNINGS AND PRECAUTIONS

警告和注意事项

Infusion-Related Reactions

输液相关反应

RYBREVANT® can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.

RYBREVANT®可引起输液相关反应（IRR）；IRR的体征和症状包括呼吸困难，潮红，发烧，发冷，恶心，胸部不适，低血压和呕吐。IRR发作的中位时间约为1小时。

RYBREVANT® with LAZCLUZE™

雷布雷万特® 与LAZCLUZE合作™

RYBREVANT® in combination with LAZCLUZE™ can cause infusion-related reactions. In MARIPOSA (n=421), IRRs occurred in 63% of patients treated with RYBREVANT® in combination with LAZCLUZE™, including Grade 3 in 5% and Grade 4 in 1% of patients. The incidence of infusion modifications due to IRR was 54% of patients, and IRRs leading to dose reduction of RYBREVANT® occurred in 0.7% of patients.

RYBREVANT®与LAZCLUZE™联合使用可引起输液相关反应。在MARIPOSA（n=421），使用RYBREVANT®联合LAZCLUZE™治疗的患者中有63%发生IRR，其中3级为5%，4级为1%。由于IRR引起的输液修改发生率为54%，导致RYBREVANT®剂量减少的IRR发生率为0.7%。

Infusion-related reactions leading to permanent discontinuation of RYBREVANT® occurred in 4.5% of patients receiving RYBREVANT® in combination with LAZCLUZE™. .

在接受RYBREVANT®联合LAZCLUZE™治疗的患者中，有4.5%发生了导致RYBREVANT®永久停药的输注相关反应。。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

In PAPILLON (n=151), infusion-related reactions occurred in 42% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, including Grade 3 (1.3%) adverse reactions. The incidence of infusion modifications due to IRR was 40%, and 0.7% of patients permanently discontinued RYBREVANT®. .

在PAPILLON（n=151）中，42%接受RYBREVANT®联合卡铂和培美曲塞治疗的患者发生输注相关反应，包括3级（1.3%）不良反应。IRR引起的输液修改发生率为40%，0.7%的患者永久停用RYBREVANT®。。

RYBREVANT® as a Single Agent

RYBREVANT®作为单一代理

In CHRYSALIS (n=302), IRR occurred in 66% of patients treated with RYBREVANT®. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4.

。在第1周第1天接受治疗的患者中，65%经历了IRR，而第2天输注的IRR发生率为3.4%，第2周输注的IRR发生率为0.4%，随后输注的IRR发生率为1.1%。在报告的内部收益率中，97%为1-2级，2.2%为3级，0.4%为4级。

The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT® due to IRR.  .

开始输注后，中位发病时间为1小时（范围0.1至18小时）。IRR引起的输液修改发生率为62%，1.3%的患者因IRR永久停用RYBREVANT®。

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT® as recommended. Administer RYBREVANT® via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions. Monitor patients for signs and symptoms of infusion reactions during RYBREVANT® infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.

术前服用抗组胺药，退热药和糖皮质激素，并按建议输注RYBREVANT®。。在有心肺复苏药物和设备的情况下，监测患者在RYBREVANT®输液过程中输液反应的体征和症状。

Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity. .

如果怀疑IRR，则中断输注。根据严重程度降低输注速度或永久停用RYBREVANT®。。

Interstitial Lung Disease/Pneumonitis

间质性肺病/肺炎

RYBREVANT® can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.

RYBREVANT®可引起严重致命的间质性肺病（ILD）/肺炎。

RYBREVANT® with LAZCLUZE™

雷布雷万特® 与LAZCLUZE合作™

In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients treated with RYBREVANT® in combination with LAZCLUZE™, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case (0.2%) of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT® and LAZCLUZE™ due to ILD/pneumonitis. .

在马里波萨，用RYBREVANT®联合LAZCLUZE™治疗的患者中有3.1%发生ILD/肺炎，其中3级为1.0%，4级为0.2%。有1例致命的ILD/肺炎病例（0.2%），2.9%的患者因ILD/肺炎而永久停用RYBREVANT®和LAZCLUZE™。。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

In PAPILLON, Grade 3 ILD/pneumonitis occurred in 2.6% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, all patients required permanent discontinuation.

在PAPILLON中，2.6%接受RYBREVANT®联合卡铂和培美曲塞治疗的患者发生3级ILD/肺炎，所有患者均需要永久停药。

RYBREVANT® as a Single Agent

RYBREVANT®作为单一代理

In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT®, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT® due to ILD/pneumonitis.

在蛹中，用RYBREVANT®治疗的患者中有3.3%发生ILD/肺炎，0.7%的患者发生3级ILD/肺炎。由于ILD/肺炎，三名患者（1%）停用了RYBREVANT®。

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). For patients receiving RYBREVANT® in combination with LAZCLUZE™, immediately withhold both drugs in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

监测患者是否出现新的或恶化的ILD/肺炎症状（例如呼吸困难，咳嗽，发烧）。对于接受RYBREVANT®联合LAZCLUZE™治疗的患者，怀疑患有ILD/肺炎的患者应立即停用这两种药物，如果确诊为ILD/肺炎，则应永久停用。

For patients receiving RYBREVANT® as a single agent or in combination with carboplatin and pemetrexed, immediately withhold RYBREVANT® in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. .

对于接受RYBREVANT®作为单一药物或与卡铂和培美曲塞联合治疗的患者，怀疑患有ILD/肺炎的患者立即停用RYBREVANT®，如果确诊为ILD/肺炎，则永久停用。。

Venous Thromboembolic (VTE) Events with Concomitant Use of RYBREVANT® and LAZCLUZE™

伴随使用RYBREVANT®和LAZCLUZE™的静脉血栓栓塞（VTE）事件

RYBREVANT® in combination with LAZCLUZE™ can cause serious and fatal venous thromboembolic (VTEs) events, including deep vein thrombosis and pulmonary embolism. The majority of these events occurred during the first four months of therapy.

RYBREVANT®联合LAZCLUZE™可导致严重致命的静脉血栓栓塞（VTEs）事件，包括深静脉血栓形成和肺栓塞。这些事件大多数发生在治疗的前四个月。

In MARIPOSA, VTEs occurred in 36% of patients receiving RYBREVANT® in combination with LAZCLUZE™, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT®, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE™; 1% of patients had VTE leading to dose reductions of RYBREVANT®, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE™; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT®, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE™.

在马里波萨，36%接受RYBREVANT®联合LAZCLUZE™治疗的患者发生VTE，其中3级患者占10%，4级患者占0.5%。在接受抗凝治疗时，1.2%的患者（n=5）发生了研究中的VTE。有两例致命的VTE病例（0.5%），9%的患者VTE导致RYBREVANT®剂量中断，7%的患者VTE导致LAZCLUZE™剂量中断；1%的患者VTE导致RYBREVANT®剂量减少，0.5%的患者VTE导致LAZCLUZE™剂量减少；3.1%的患者VTE导致RYBREVANT®永久停药，1.9%的患者VTE导致LAZCLUZE™永久停药。

The median time to onset of VTEs was 84 days (range: 6 to 777). .

VTE发作的中位时间为84天（范围：6至777）。。

Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE events and treat as medically appropriate.

在治疗的前四个月进行预防性抗凝治疗。不建议使用维生素K拮抗剂。监测VTE事件的体征和症状，并根据医学情况进行治疗。

Withhold RYBREVANT® and LAZCLUZE™ based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT® and LAZCLUZE™ at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT® and continue treatment with LAZCLUZE™ at the same dose level at the discretion of the healthcare provider. .

根据严重程度扣留RYBREVANT®和LAZCLUZE™。一旦开始抗凝治疗，由医疗保健提供者自行决定恢复相同剂量的RYBREVANT®和LAZCLUZE™治疗。尽管进行了治疗性抗凝治疗，但如果VTE复发，则永久停用RYBREVANT®，并由医疗保健提供者自行决定以相同的剂量水平继续使用LAZCLUZE™治疗。。

Dermatologic Adverse Reactions

皮肤科不良反应

RYBREVANT® can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin.

RYBREVANT®可引起严重皮疹，包括中毒性表皮坏死松解症（TEN）、痤疮样皮炎、瘙痒和皮肤干燥。

RYBREVANT® with LAZCLUZE™

雷布雷万特® 与LAZCLUZE合作™

In MARIPOSA, rash occurred in 86% of patients treated with RYBREVANT® in combination with LAZCLUZE™, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT® and 30% for LAZCLUZE™, rash leading to dose reductions occurred in 23% of patients for RYBREVANT® and 19% for LAZCLUZE™, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT® and 1.7% for LAZCLUZE™.  .

在马里波萨，使用RYBREVANT®联合LAZCLUZE™治疗的患者中有86%出现皮疹，其中26%的患者出现3级皮疹。皮疹发作的中位时间为14天（范围：1至556天）。导致剂量中断的皮疹发生在37%的RYBREVANT®患者和30%的LAZCLUZE™患者中，导致剂量减少的皮疹发生在23%的RYBREVANT®患者和19%的LAZCLUZE™患者中，导致永久停药的皮疹发生在5%的RYBREVANT®患者和1.7%的LAZCLUZE™患者中。。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

In PAPILLON, rash occurred in 89% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, including Grade 3 (19%) adverse reactions. Rash leading to dose reductions occurred in 19% of patients, and 2% permanently discontinued RYBREVANT® and 1.3% discontinued pemetrexed.  .

在PAPILLON中，89%接受RYBREVANT®联合卡铂和培美曲塞治疗的患者出现皮疹，包括3级（19%）不良反应。19%的患者出现皮疹导致剂量减少，2%的患者永久停用RYBREVANT®和1.3%的患者停用培美曲塞。。

RYBREVANT® as a Single Agent

RYBREVANT®作为单一代理

In CHRYSALIS, rash occurred in 74% of patients treated with RYBREVANT® as a single agent, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT® was permanently discontinued due to rash in 0.7% of patients. .

在蛹中，使用RYBREVANT®作为单一药物治疗的患者中有74%出现皮疹，其中3.3%的患者出现3级皮疹。皮疹发作的中位时间为14天（范围：1至276天）。。。

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT® as a single agent.

。

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT® or LAZCLUZE™ in combination with RYBREVANT®. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin. .

指导患者在使用RYBREVANT®或LAZCLUZE™联合RYBREVANT®治疗期间和治疗后2个月内限制阳光照射。建议患者穿防护服并使用广谱UVA/UVB防晒霜。干性皮肤建议使用不含酒精（例如不含异丙醇、不含乙醇）的润肤霜。。

When initiating RYBREVANT® treatment with or without LAZCLUZE™, administer alcohol-free emollient cream to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (e.g. use of oral antibiotics) to reduce the risk of dermatologic reactions. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics.

在开始使用或不使用LAZCLUZE™的RYBREVANT®治疗时，使用无酒精润肤霜以降低皮肤病不良反应的风险。考虑采取预防措施（例如使用口服抗生素）以降低皮肤病反应的风险。如果出现皮肤反应，开始局部使用皮质类固醇以及局部和/或口服抗生素。

For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT® in combination with LAZCLUZE™, withhold, dose reduce or permanently discontinue both drugs based on severity.

对于3级反应，添加口服类固醇并考虑皮肤科咨询。立即将出现严重皮疹，不典型外观或分布或2周内缺乏改善的患者转诊给皮肤科医生。对于接受RYBREVANT®联合LAZCLUZE™治疗的患者，根据严重程度扣留，减少剂量或永久停用两种药物。

For patients receiving RYBREVANT® as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT® based on severity. .

对于接受RYBREVANT®作为单一药物或与卡铂和培美曲塞联合治疗的患者，根据严重程度停止，剂量减少或永久停用RYBREVANT®。。

Ocular Toxicity

眼部毒性

RYBREVANT® can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis.

RYBREVANT®可引起眼部毒性，包括角膜炎、睑缘炎、干眼症、结膜发红、视力模糊、视力障碍、眼部瘙痒、眼睛瘙痒和葡萄膜炎。

RYBREVANT® with LAZCLUZE™

雷布雷万特® 与LAZCLUZE合作™

In MARIPOSA, ocular toxicity occurred in 16% of patients treated with RYBREVANT® in combination with LAZCLUZE™, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT® and continue LAZCLUZE™ based on severity.

在马里波萨，用RYBREVANT®联合LAZCLUZE™治疗的患者中有16%发生眼部毒性，其中0.7%的患者出现3级或4级眼部毒性。根据严重程度，扣留、减少剂量或永久停用RYBREVANT®并继续使用LAZCLUZE™治疗。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

In PAPILLON, ocular toxicity including blepharitis, dry eye, conjunctival redness, blurred vision, and eye pruritus occurred in 9%. All events were Grade 1-2.

在PAPILLON中，9%发生眼部毒性，包括睑缘炎，干眼症，结膜发红，视力模糊和眼睛瘙痒。所有事件均为1-2级。

RYBREVANT® as a Single Agent

RYBREVANT®作为单一代理

In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT®. All events were Grade 1-2.

在蛹中，角膜炎发生率为0.7%，葡萄膜炎发生率为0.3%。所有事件均为1-2级。

Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT® based on severity.

及时将眼部症状新发或恶化的患者转诊给眼科医生。根据严重程度扣留、减少剂量或永久停用RYBREVANT®。

Embryo-Fetal Toxicity

胚胎-胎儿毒性

Based on its mechanism of action and findings from animal models, RYBREVANT® and LAZCLUZE™ can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus.

。告知女性生殖潜力对胎儿的潜在风险。

Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT®.

建议有生殖潜力的女性患者在治疗期间和最后一剂RYBREVANT®后3个月内使用有效的避孕措施。

Advise females of reproductive potential to use effective contraception during treatment with LAZCLUZE™ and for 3 weeks after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with LAZCLUZE™ and for 3 weeks after the last dose. .

建议有生殖潜力的女性在使用LAZCLUZE™治疗期间和最后一剂后3周内使用有效的避孕措施。建议有生殖潜能的女性伴侣的男性患者在LAZCLUZE™治疗期间和最后一剂后3周内使用有效的避孕措施。。

Adverse Reactions

不良反应

RYBREVANT® with LAZCLUZE™

雷布雷万特® 与LAZCLUZE合作™

For the 421 patients in the MARIPOSA clinical trial who received RYBREVANT® in combination with LAZCLUZE™, the most common adverse reactions (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (RYBREVANT®, 63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), nausea (21%), and ocular toxicity (16%).

对于接受RYBREVANT®联合LAZCLUZE™治疗的MARIPOSA临床试验中的421名患者，最常见的不良反应（≥20%）是皮疹（86%），指甲毒性（71%），输注相关反应（RYBREVANT®，63%），肌肉骨骼疼痛（47%），口腔炎（43%），水肿（43%），VTE（36%），感觉异常（35%），疲劳（32%），腹泻（31%），便秘（29%），新型冠状病毒肺炎（26%），出血（25%），皮肤干燥（25%），食欲下降（24%），瘙痒（24%），恶心（21%）和眼部毒性（16%）。

The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%). .

最常见的3或4级实验室异常（≥2%）是白蛋白降低（8%），钠降低（7%），ALT升高（7%），钾降低（5%），血红蛋白降低（3.8%），AST升高（3.8%），GGT升高（2.6%）和镁升高（2.6%）。。

Serious adverse reactions occurred in 49% of patients who received RYBREVANT® in combination with LAZCLUZE™. Serious adverse reactions occurring in ≥2% of patients included VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and infusion-related reaction (RYBREVANT®) (2.1% each).

49%接受RYBREVANT®联合LAZCLUZE™治疗的患者发生严重不良反应。≥2%的患者发生严重不良反应，包括VTE（11%），肺炎（4%），ILD/肺炎和皮疹（各2.9%），COVID-19（2.4%），胸腔积液和输液相关反应（RYBREVANT®）（各2.1%）。

Fatal adverse reactions occurred in 7% of patients who received RYBREVANT® in combination with LAZCLUZE™ due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each). .

7%接受RYBREVANT®联合LAZCLUZE™治疗的患者发生致命不良反应，原因是死亡未另行说明（1.2%）；败血症和呼吸衰竭（各1%）；肺炎，心肌梗塞和猝死（各0.7%）；脑梗死，肺栓塞（PE）和COVID-19感染（各0.5%）；和ILD/肺炎，急性呼吸窘迫综合征（ARDS）和心肺骤停（各0.2%）。。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

For the 151 patients in the PAPILLON clinical trial who received RYBREVANT® in combination with carboplatin and pemetrexed, the most common adverse reactions (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), infusion-related reaction (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%).

对于接受RYBREVANT®联合卡铂和培美曲塞治疗的151名PAPILLON临床试验患者，最常见的不良反应（≥20%）是皮疹（90%），指甲毒性（62%），口腔炎（43%），输注相关反应（42%），疲劳（42%），水肿（40%），便秘（40%），食欲下降（36%），恶心（36%），新型冠状病毒肺炎（24%），腹泻（21%）和呕吐（21%）。

The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%). .

最常见的3至4级实验室异常（≥2%）是白蛋白减少（7%），丙氨酸氨基转移酶增加（4%），γ-谷氨酰转移酶增加（4%），钠减少（7%），钾减少（11%），镁减少（2%），白细胞减少（17%），血红蛋白（11%），中性粒细胞（36%），血小板（10%）和淋巴细胞（11%）。。

Serious adverse reactions occurred in 37% of patients who received RYBREVANT® in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified. .

37%接受RYBREVANT®联合卡铂和培美曲塞治疗的患者发生严重不良反应。≥2%的患者出现严重不良反应，包括皮疹、肺炎、ILD、肺栓塞、呕吐和新型冠状病毒肺炎。由于肺炎，脑血管意外，心肺骤停，新型冠状病毒肺炎，败血症和未另行说明的死亡，7例患者（4.6%）发生致命不良反应。。

RYBREVANT® as a Single Agent

RYBREVANT®作为单一代理

For the 129 patients in the CHRYSALIS clinical trial who received RYBREVANT® as a single agent, the most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%).

对于接受RYBREVANT®作为单一药物的CHRYSALIS临床试验中的129名患者，最常见的不良反应（≥20%）是皮疹（84%），IRR（64%），甲沟炎（50%），肌肉骨骼疼痛（47%），呼吸困难（37%），恶心（36%），疲劳（33%），水肿（27%），口腔炎（26%），咳嗽（25%），便秘（23%）和呕吐（22%）。

The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%). .

最常见的3至4级实验室异常（≥2%）是淋巴细胞减少（8%），白蛋白减少（8%），磷酸盐减少（8%），钾减少（6%），碱性磷酸酶增加（4.8%），葡萄糖增加（4%），γ-谷氨酰转移酶增加（4%），钠减少（4%）。。

Serious adverse reactions occurred in 30% of patients who received RYBREVANT®. Serious adverse reactions in ≥2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death. .

接受RYBREVANT®治疗的患者中有30%发生严重不良反应。。2例（1.5%）因肺炎发生致命不良反应，1例（0.8%）因猝死发生致命不良反应。。

LAZCLUZE™ Drug Interactions

LAZCLUZE™药物相互作用

Avoid concomitant use of LAZCLUZE™ with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.

避免将LAZCLUZE™与强效和中度CYP3A4诱导剂同时使用。考虑另一种不可能诱导CYP3A4的伴随药物。

Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.

按照批准的CYP3A4或BCRP底物产品标签中的建议，监测与CYP3A4或BCRP底物相关的不良反应，其中最小的浓度变化可能导致严重的不良反应。

Please read full Prescribing Information for RYBREVANT®.

请阅读RYBREVANT®的完整处方信息。

Please read full Prescribing Information for LAZCLUZE™.

请阅读LAZCLUZE™的完整处方信息。

About Johnson & Johnson

关于强生公司

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

在强生公司，我们相信健康就是一切。我们在医疗保健创新方面的优势使我们能够建立一个预防、治疗和治愈复杂疾病的世界，在这个世界上，治疗更加智能，侵入性更小，解决方案更加个性化。通过我们在创新医学和医学技术方面的专业知识，我们拥有独特的优势，可以在今天的所有医疗保健解决方案中进行创新，以实现明天的突破，并深刻影响人类的健康。

Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc. are Johnson & Johnson companies. .

了解更多信息，请访问https://www.jnj.com/或访问www.janssen.com/johnson-johnson-innovative-medicine。请访问@JanssenUS和@JNJInnovMed。Janssen Research&Development，LLC和Janssen Biotech，Inc.是强生公司。。

Cautions Concerning Forward-Looking Statements

关于前瞻性陈述的注意事项

This press release contains 'forward-looking statements' as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of RYBREVANT® (amivantamab-vmjw) and LAZCLUZE™ (lazertinib). The reader is cautioned not to rely on these forward-looking statements.

本新闻稿包含1995年《私人证券诉讼改革法案》中定义的“前瞻性声明”，涉及RYBREVANT®（amivantamab vmjw）和LAZCLUZE™（lazertinib）的产品开发以及潜在益处和治疗影响。提醒读者不要依赖这些前瞻性陈述。

These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections Janssen Research & Development, LLC, Janssen Biotech, Inc.

这些声明基于当前对未来事件的预期。如果基础假设被证明不准确或已知或未知的风险或不确定性出现，实际结果可能与Janssen Research&Development，LLC，Janssen Biotech，Inc.的预期和预测有很大差异。

and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment.

和/或强生公司。风险和不确定性包括但不限于：产品研发固有的挑战和不确定性，包括临床成功和获得监管批准的不确定性；商业成功的不确定性；制造困难和延误；竞争，包括技术进步、新产品和竞争对手获得的专利；专利面临的挑战；导致产品召回或监管行动的产品功效或安全问题；医疗保健产品和服务购买者的行为和支出模式的变化；；以及医疗保健成本控制的趋势。

A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned 'Cautionary Note Regarding Forward-Looking Statements' and 'Item 1A. Risk Factors,' and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities.

有关这些风险、不确定性和其他因素的更多列表和描述，请参见强生公司截至2023年12月31日的10-K表年度报告，包括标题为“关于前瞻性声明的注意事项”和“项目1A”的章节。以及强生公司随后在10-Q表上的季度报告和其他提交给证券的文件中。

*Dr. Shirish M. Gadgeel has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

*博士。Shirish M.Gadgeel为强生公司提供咨询、咨询和演讲服务；他没有收到任何媒体工作的报酬。

†See the NCCN Guidelines for detailed recommendations, including other treatment options.

†有关详细建议，包括其他治疗方案，请参阅NCCN指南。

‡The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

‡NCCN非小细胞肺癌指南为某些应该测试的个体生物标志物提供了建议，并推荐了测试技术，但不认可任何特定的商业生物标志物检测或商业实验室。

§The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way..

§NCCN内容不构成医疗建议，不应代替执业医师寻求专业医疗建议、诊断或治疗。NCCN对其内容、使用或应用不作任何形式的保证，也不以任何方式对其应用或使用承担任何责任。。

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1 Gadgeel SM, et al. Amivantamab Plus LAZCLUZE™ vs Osimertinib in First-line EGFR-mutant Advanced NSCLC: Longer Follow-up of the MARIPOSA Study. IASLC WCLC 2024. September 8, 2024.

1 Gadgeel SM等人。Amivantamab加LAZCLUZE™与Osimertinib在一线EGFR突变晚期NSCLC中的对比：MARIPOSA研究的更长时间随访。。2024年9月8日。

2Cho BC, et al. Amivantamab Plus LAZCLUZE™ vs Osimertinib as First-line Treatment in Patients With EGFR-mutated, Advanced Non-small Cell Lung Cancer (NSCLC): Primary Results From MARIPOSA, a Phase 3, Global, Randomized, Controlled Trial. 2023 European Society for Medical Oncology. October 23, 2023.

2Cho BC等人。Amivantamab加LAZCLUZE™与Osimertinib作为EGFR突变的晚期非小细胞肺癌（NSCLC）患者的一线治疗：MARIPOSA的主要结果，这是一项3期全球随机对照试验。2023年欧洲肿瘤内科学会。2023年10月23日。

3 ClinicalTrials.gov. A Study of Amivantamab and LAZCLUZE™ Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed September 2024.

。网址：https://classic.clinicaltrials.gov/ct2/show/NCT04487080.2024年9月访问。

4 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

4 RYBREVANT®处方信息。宾夕法尼亚州霍沙姆：杨森生物技术公司。

5 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.1.2024© National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed September 2024..

5经NCCN非小细胞肺癌临床实践指南（NCCN Guidelines®）第1.2024版许可引用©National Comprehensive Cancer Network，Inc.保留所有权利。要查看指南的最新完整版本，请在线访问NCCN.org。2024年9月访问。。

6 ClinicalTrials.gov. A Study of Amivantamab and LAZCLUZE™ in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2).

6 ClinicalTrials.gov。在Osimertinib失败后表皮生长因子受体（EGFR）突变的局部晚期或转移性非小细胞肺癌患者（MARIPOSA-2）中，Amivantamab和LAZCLUZE™联合铂类化疗与铂类化疗的研究。

Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed September 2024..

网址：https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295.2024年9月访问。。

7 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664.

7 ClinicalTrials.gov。一项以表皮生长因子受体（EGFR）外显子20插入（PAPILLON）为特征的晚期或转移性非小细胞肺癌患者与卡铂-培美曲塞相比，阿米万塔单抗和卡铂-培美曲塞联合治疗的研究。网址：https://clinicaltrials.gov/ct2/show/NCT04538664.

Accessed September 2024..

2024年9月访问。。

8 ClinicalTrials.gov. A Study of LAZCLUZE™ With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed September 2024..

8 ClinicalTrials.gov。在表皮生长因子受体（EGFR）突变的晚期或转移性非小细胞肺癌（PALOMA-3）参与者中，皮下注射阿米万塔单抗与静脉注射阿米万塔单抗的LAZCLUZE™研究。https://clinicaltrials.gov/ct2/show/NCT05388669.2024年9月访问。。

9 ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed September 2024.

9 ClinicalTrials.gov。阿米万塔单抗在晚期或转移性实体瘤（包括表皮生长因子受体（EGFR）突变的非小细胞肺癌（PALOMA-2））参与者中的研究。https://clinicaltrials.gov/ct2/show/NCT05498428.2024年9月访问。

10 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/study/NCT04606381. Accessed September 2024.

。网址：https://clinicaltrials.gov/study/NCT04606381.2024年9月访问。

11 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed September 2024.

11 ClinicalTrials.gov。一项针对晚期非小细胞肺癌（CHRYSALIS）参与者的人类双特异性EGFR和cMet抗体阿米万塔单抗的研究。（笑声）https://clinicaltrials.gov/ct2/show/NCT02609776.2024年9月访问。

12 ClinicalTrials.gov. A Study of LAZCLUZE™ as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed September 2024.

12 ClinicalTrials.gov。LAZCLUZE™作为单一疗法或与阿米万塔单抗联合用于晚期非小细胞肺癌（CHRYSALIS-2）参与者的研究。（笑声）https://clinicaltrials.gov/ct2/show/NCT04077463.2024年9月访问。

13 ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed September 2024.

13 ClinicalTrials.gov。Amivantamab和Capmatinib联合治疗不可切除的转移性非小细胞肺癌（METalmark）的研究。（笑声）https://clinicaltrials.gov/ct2/show/NCT05488314.2024年9月访问。

14 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1. Accessed September 2024.

14 ClinicalTrials.gov。一项关于阿米万塔单抗和西曲单抗联合治疗转移性非小细胞肺癌（PolyDamas）参与者的研究。（笑声）https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1.2024年9月访问。

15 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed September 2024.

15 ClinicalTrials.gov。术前用药，以减少阿米万塔单抗相关的输注相关反应（SKIPPirr）。（笑声）https://classic.clinicaltrials.gov/ct2/show/NCT05663866.2024年9月访问。

16 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Docetaxel in Participants With Metastatic Non-small Cell Lung Cancer (swalloWTail). https://www.clinicaltrials.gov/study/NCT06532032?term=Swallowtail&intr=amivantamab&rank=1. Accessed September 2024.

16 ClinicalTrials.gov。一项关于阿米万塔单抗和多西紫杉醇联合治疗转移性非小细胞肺癌（燕尾型）参与者的研究。https://www.clinicaltrials.gov/study/NCT06532032?term=Swallowtail&intr=amivantamab&rank=1.2024年9月访问。

17 ClinicalTrials.gov. A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer (OrigAMI-1). https://clinicaltrials.gov/study/NCT05379595?term=NCT05379595&rank=1. Accessed September 2024.

17 ClinicalTrials.gov。对晚期或转移性结直肠癌（OrigAMI-1）参与者进行阿米万塔单抗单药治疗以及标准化疗的研究。https://clinicaltrials.gov/study/NCT05379595?term=NCT05379595&rank=1.2024年9月访问。

18 ClinicalTrials.gov. A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Recurrent/ Metastatic Head and Neck Cancer (OrigAMI-4). https://clinicaltrials.gov/study/NCT06385080?term=OrigAMI-4&limit=10&rank=1. Accessed September 2024.

18 ClinicalTrials.gov。对复发/转移性头颈癌（折纸-4）参与者单独或除其他治疗药物外的阿米万塔单抗的研究。https://clinicaltrials.gov/study/NCT06385080?term=OrigAMI-4&极限=10&等级=1。2024年9月访问。

19 The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed September 2024.

19世界卫生组织。癌症。（笑声）https://www.who.int/news-room/fact-sheets/detail/cancer.2024年9月访问。

20 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed September 2024.

20美国癌症协会。什么是肺癌？（笑声）https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html.2024年9月访问。

21 Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18.

21 Oxnard JR等人。携带EGFR外显子20插入的肺癌的自然史和分子特征。J胸部肿瘤学。2013年2月；8（2）：179-84。doi:10.1097/JTO.0b013e3182779d18。

22 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.

22 Bauml JM等人。EGFR外显子20插入突变变体的诊断不足：基于NGS的真实数据集的估计。摘要发表于：世界肺癌年会；2021年1月29日；新加坡。

23 Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 37:97-104.

23 Pennell NA等人。辅助厄洛替尼治疗切除的表皮生长因子受体突变型非小细胞肺癌患者的II期临床试验。J临床肿瘤学。37:97-104。

24 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.

24 Burnett H等人。晚期非小细胞肺癌中EGFR外显子20插入的流行病学和临床负担：系统文献综述。摘要发表于：世界肺癌年会；2021年1月29日；新加坡。

25 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993.

25 Zhang YL等。非小细胞肺癌患者EGFR突变的患病率：系统评价和荟萃分析。Oncotarget。2016年；7（48）：78985-78993。

26 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911.

26 Midha A等人。腺癌组织学中非小细胞肺癌的EGFR突变发生率：系统综述和种族全球地图。Am J Cancer Res.2015；5（9）：2892-2911。

27 American Lung Association. EGFR and Lung Cancer. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed March 2024.

27美国肺协会。EGFR和肺癌。https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr.2024年3月访问。

28 Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site.

。马里兰州贝塞斯达，https://seer.cancer.gov/csr/1975_2016/根据2018年11月SEER数据提交，发布到SEER网站。

29 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65.

29 Lin JJ等。用EGFR-TKIs治疗的EGFR突变转移性肺腺癌的五年生存率。J胸部肿瘤学。2016年4月；11（4）：556-65。

30 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9.

30 Arcila，M。等人。肺腺癌中的EGFR外显子20插入突变：患病率，分子异质性和临床病理特征。摩尔癌症治疗。2013年2月；12（2）：220-9。

31 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.

31 Girard N等人。携带EGFR外显子20插入突变和常见EGFR突变的NSCLC患者的比较临床结果。摘要发表于：世界肺癌年会；2021年1月29日；新加坡。

32 LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

32 LAZCLUZE™处方信息。宾夕法尼亚州霍沙姆：杨森生物技术公司。

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investor-relations@its.jnj.com

Jackie Zima-Evans

杰基[UNK]齐玛·埃文斯

U.S. Medical Inquiries

U、 美国医疗查询

jzimaev@ITS.JNJ.com

jzimaev@ITS.JNJ.com

+1 800 526-7736

+1 800 526-7736

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SOURCE Johnson & Johnson