Post-progression outcomes showed significant and sustained improvement for RYBREVANT® plus standard of care versus chemotherapy alone

进展后结果显示，与单独化疗相比，RYBREVANT®plus标准治疗显着且持续改善

BARCELONA, Sept. 14, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) today announced updated results from the Phase 3 MARIPOSA-2 study which showed RYBREVANT® (amivantamab-vmjw) combined with chemotherapy led to consistent benefit across post-progression outcomes in adult patients with previously treated non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations.

巴塞罗那，2024年9月14日/PRNewswire/--强生公司（纽约证券交易所：JNJ）今天宣布了第三阶段MARIPOSA-2研究的最新结果，该研究显示RYBREVANT®（amivantamab vmjw）联合化疗可使先前接受过表皮生长因子受体（EGFR）外显子19缺失（ex19del）或L858R替代突变治疗的非小细胞肺癌（NSCLC）成年患者的进展后结局持续获益。

The data also reveal a favorable trend toward improved overall survival (OS) compared to chemotherapy alone. Results were presented at the European Society of Medical Oncology (ESMO) 2024 Congress.1.

数据还显示，与单独化疗相比，总体生存率（OS）有所提高。结果发表在欧洲肿瘤内科学会（ESMO）2024年大会上。

'The positive overall survival trend seen in MARIPOSA-2 is incredibly promising, suggesting that amivantamab combined with chemotherapy could potentially change the treatment landscape for a population that has historically faced limited options,' said Prof. Sanjay Popat, FRCP, Ph.D., medical oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in the United Kingdom, and presenting author.* 'Building on the strong progression-free survival data previously reported from this study and by helping more patients stay on treatment for longer, we are improving their chances for better outcomes.'.

英国皇家马斯登医院和癌症研究所的医学肿瘤学家、FRCP博士桑杰·波帕特教授（SanjayPopat）表示：“马里波萨-2的总体生存率呈上升趋势，前景令人难以置信，这表明阿米万塔单抗联合化疗可能会改变一个历史上选择有限的人群的治疗前景。”他是本文作者。*“基于本研究先前报道的强大的无进展生存数据，通过帮助更多患者延长治疗时间，我们正在改善他们获得更好结果的机会。”。

At the second interim analysis, with a median follow-up of 18.1 months, 50 percent of patients treated with RYBREVANT® plus chemotherapy were still alive at the 18-month landmark, compared to 40 percent of those receiving chemotherapy alone (median OS, 17.7 vs 15.3 months, respectively; hazard ratio [HR], 0.73; [95 percent confidence interval [CI], 0.54–0.99]; nominal P=0.039).

。

RYBREVANT® plus chemotherapy showed a significant improvement in treatment discontinuation rates, with nearly five times as many patients remaining on therapy at 18 months (22 percent) compared to chemotherapy (4 percent) (median time to treatment discontinuation [TTD], 10.4 vs 4.5 months, respectively; HR, 0.42; [95 percent CI, 0.33–0.53]; nominal P<0.0001).

。

Additionally, patients treated with RYBREVANT® plus chemotherapy experienced a 27 percent reduction in the risk of symptomatic progression (median time to symptomatic progression [TTSP], 16.0 vs 11.8 months; HR, 0.73; [95 percent CI, 0.55–0.96]; nominal P=0.026). The time to subsequent therapy was significantly prolonged with the RYBREVANT® combination compared to chemotherapy (median time to subsequent therapy [TTST], 12.2 vs 6.6 months, respectively; HR, 0.51; [95 percent CI, 0.39–0.65]; nominal P<0.0001), which also reduced the risk of second disease progression or death by 36 percent (medan progression-free survival [PFS2], 16.0 vs 11.6 months, respectively; HR, 0.64; [95 percent CI, 0.48–0.85]; nominal P=0.002).1.

此外，接受RYBREVANT®联合化疗的患者症状进展的风险降低了27%（症状进展的中位时间[TTSP]，16.0比11.8个月；HR，0.73；[95%可信区间，0.55-0.96]；标称P=0.026）。与化疗相比，RYBREVANT®联合治疗的后续治疗时间显着延长（后续治疗的中位时间[TTST]，分别为12.2和6.6个月；HR，0.51；[95%CI，0.39-0.65]；标称P<0.0001），这也将第二次疾病进展或死亡的风险降低了36%（medan无进展生存期[PFS2]，分别为16.0和11.6个月；HR，0.64；[95%CI，0.48-0.85]；标称P=0.002）。

In the MARIPOSA-2 study, the safety profile of RYBREVANT® in combination with chemotherapy was consistent with the established profiles of the individual treatments. Permanent discontinuation of RYBREVANT® due to adverse reactions occurred in 11 percent of patients.2

在MARIPOSA-2研究中，RYBREVANT®联合化疗的安全性与个体治疗的既定特征一致。11%的患者因不良反应而永久停用RYBREVANT®。2

'We are pleased to see that RYBREVANT plus chemotherapy continues to show improved survival outcomes after a year and a half of follow-up, providing real benefits to patients with few other options,' said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine.

强生创新医学（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）医学博士说：“我们很高兴看到，经过一年半的随访，RYBREVANT plus化疗继续显示出改善的生存结果，为几乎没有其他选择的患者提供了真正的益处。”。

'These results underscore the potential of this combination regimen to make a meaningful difference for patients, and we anticipate continued improvement as we move toward the final analysis.'.

“这些结果强调了这种联合治疗方案对患者产生有意义影响的潜力，我们预计随着最终分析的进行，情况会持续改善。”。

RYBREVANT® plus chemotherapy received approval by the European Commision in August 2024 as a treatment for patients with previously treated NSCLC with common EGFR mutations based on the superior efficacy and safety profile demonstrated in this study.

RYBREVANT®plus化疗于2024年8月获得欧洲委员会的批准，用于治疗先前治疗过的具有常见EGFR突变的NSCLC患者，这是基于本研究证明的优越疗效和安全性。

About the MARIPOSA-2 Study

关于MARIPOSA-2研究

MARIPOSA-2 (NCT04988295) is a randomized, open-label Phase 3 study evaluating the efficacy and safety of two regimens of RYBREVANT® (with and without LAZCLUZE™) and chemotherapy. Patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after osimertinib were randomized to treatment with RYBREVANT® plus chemotherapy, RYBREVANT® plus chemotherapy with LAZCLUZE™, or chemotherapy alone.

MARIPOSA-2（NCT04988295）是一项随机，开放标签的3期研究，评估RYBREVANT®（有和没有LAZCLUZE TM）和化疗两种方案的疗效和安全性。局部晚期或转移性EGFR ex19del或L858R替代NSCLC患者在osimertinib时或之后有疾病进展，随机接受RYBREVANT®加化疗，RYBREVANT®加LAZCLUZE™化疗或单独化疗。

The dual primary endpoint was used to compare the progression-free survival (PFS) (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR) for each experimental arm to chemotherapy alone. Secondary endpoints included objective response as assessed by BICR, OS, duration of response (DoR), time to subsequent therapy, PFS after first subsequent therapy (PFS2) and intracranial PFS.

双主要终点用于比较无进展生存期（PFS）（使用RECIST v1.1指南），通过盲法独立中央评估（BICR）评估每个实验组与单独化疗。次要终点包括通过BICR，OS，反应持续时间（DoR），随后治疗的时间，首次随后治疗后的PFS（PFS2）和颅内PFS评估的客观反应。

All study participants underwent serial brain imaging to allow for the robust assessment of intracranial endpoints, and to assess the central nervous system (CNS) activity of RYBREVANT® with and without LAZCLUZE™. As brain metastases can lead to significant burden and poor outcomes for patients, this aspect of the study design provides critical information in an area of high unmet need.

所有研究参与者均接受了连续脑成像，以对颅内终点进行可靠评估，并评估有无LAZCLUZE™的RYBREVANT®的中枢神经系统（CNS）活性。由于脑转移可能导致患者的重大负担和不良后果，因此研究设计的这一方面在高度未满足需求的领域提供了关键信息。

The study enrolled 657 patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after osimertinib.3.

该研究纳入了657例局部晚期或转移性EGFR ex19del或L858R替代NSCLC患者，他们在osimertinib时或之后有疾病进展。

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..

2023年11月，强生公司向美国FDA提交了一份补充生物制剂许可证申请（sBLA），用于RYBREVANT®联合化疗治疗EGFR突变的非小细胞肺癌患者，这些患者根据MARIPOSA-2研究在osimertinib上或之后进展。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。还向EMA提交了RYBREVANT®营销授权扩展（线路扩展）的申请，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 lazertinib (LAZCLUZE™) as a Category 1 recommendation for first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.5 †‡Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a Category 1 recommendation 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 Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a 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 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 MARIPOSA-2 study, RYBREVANT® is being studied in multiple clinical trials, including:.

Amivantamab vmjw（RYBREVANT®）加拉泽替尼（LAZCLUZE™）作为EGFR外显子19缺失或外显子21 L858R突变的局部晚期或转移性NSCLC患者一线治疗的1类推荐药物。5†‡Amivantamab vmjw（RYBREVANT®）加化疗作为局部晚期或转移性NCSLC患者的1类推荐药物，EGFR外显子19缺失或外显子21 L858R突变患者在接受osimertinib治疗后出现疾病进展。5†‡Amivantamab vmjw（Rybrevantamab®）对于新诊断的晚期或转移性EGFR外显子20插入突变阳性晚期非小细胞肺癌初治患者，加用卡铂和培美曲塞作为一线治疗的1类推荐药物，对于铂类化疗后或铂类化疗后有进展或无免疫治疗且EGFR外显子20插入突变阳性的晚期非小细胞肺癌患者，作为2A类推荐药物。5†‡Amivantamab vmjw（RYBREVANT®）作为2A类推荐，对于在铂类化疗或铂类化疗后进行或未进行免疫治疗且EGFR外显子20插入突变阳性NSCLC的患者。5†‡除MARIPOSA-2研究外，RYBREVANT®正在多项临床试验中进行研究，包括：。

The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT® in combination with LAZCLUZE™ versus osimertinib and versus LAZCLUZE™ alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.6• The 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 mutations.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 first-dose infusion-related r.

3期MARIPOSA（NCT04487080）研究评估了RYBREVANT®联合LAZCLUZE™与osimertinib以及单独使用LAZCLUZE™治疗EGFR ex19del或L858R替代突变的局部晚期或转移性NSCLC患者的一线治疗。6•3期PAPILLON（NCT04538664）研究评估了RYBREVANT®联合卡铂-培美曲塞与单独化疗治疗EGFR外显子20插入突变的晚期或转移性NSCLC患者的一线治疗。7 3期PALOMA-3（NCT05388669）研究评估了Lazclc在EGFR突变的晚期或转移性NSCLC患者中，皮下注射阿米万塔单抗的Luze™与静脉注射阿米万塔单抗相比。8 2期PALOMA-2（NCT05498428）研究评估了包括EGFR突变的NSCLC在内的晚期或转移性实体瘤患者的皮下阿米万塔单抗。9 1期PALOMA（NCT04606381）研究基于安全性和药代动力学评估皮下给药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评估RYBREVANT®联合LAZCLUZE™和LAZCLUZE™的1/1b期蛹-2（NCT04077463）研究评估RYBREVANT®联合LAZCLUZE™和LAZCLUZE™作为EGFR突变晚期非小细胞肺癌患者的单一疗法。12评估RYBREVANT®和卡马替尼的1/2期METalmark（NCT05488314）研究局部晚期或转移性非小细胞肺癌的联合治疗[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）探讨了如何降低首次剂量输注相关r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..

2023年，《临床肿瘤学杂志》发表了LAZCLUZE™3期LASER301研究的疗效和安全性分析。。

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.19,20,23,24,25,26 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，NSCLC占所有肺癌病例的80%至85%。19,20 NSCLC的主要亚型是腺癌，鳞状细胞癌和大细胞癌。21 NSCLC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NSCLC腺癌组织学患者中，发生在40%至50%的亚洲患者中。19,20,23,24,25,26 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例EGFR外显子20插入突变患者的实际五年总生存率（OS）在一线环境中占8%，这比EGFR ex19del或L858R突变患者更差，后者的实际五年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.

在蛹（n=302）中，66%接受RYBREVANT®治疗的患者发生IRR。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®。在第1周和第2周通过外周线给予RYBREVANT®，以降低输液相关反应的风险。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。三名患者（1%）因ILD/肺炎停止服用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.

。对于接受RYBREVANT®联合LAZCLUZE™治疗的患者，怀疑患有ILD/肺炎的患者立即停用这两种药物，如果确诊为ILD/肺炎，则永久停用。

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。。

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）。5%的患者出现皮疹导致剂量减少，0.7%的患者因皮疹而永久停用RYBREVANT®。。

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

用RYBREVANT®作为单一药物治疗的一名患者（0.3%）发生中毒性表皮坏死松解。

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，服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，根据严重程度扣留、减少剂量或永久停用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。扣留、减少剂量或永久停用RYBREVANT®并根据严重程度继续使用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.

根据其作用机制和动物模型的发现，RYBREVANT®和LAZCLUZE™给孕妇服用时会导致胎儿伤害。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%).

。

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™治疗的患者因死亡而发生致命不良反应（1.2%）；败血症和呼吸衰竭（各1%）；肺炎，心肌梗塞和猝死（各0.7%）；；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%的患者出现严重不良反应，包括肺栓塞，肺炎/ILD，呼吸困难，肌肉骨骼疼痛，肺炎和肌肉无力。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/。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 of 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，包括竞争对手取得的技术进步、新产品和专利；专利面临的挑战；；医疗保健产品和服务购买者的行为和支出模式的变化；适用法律法规的变更，包括全球医疗保健改革；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 Securit.

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“关于前瞻性声明的警示说明”和“项目1A”的章节。“风险因素”，以及强生公司随后在10-Q表上的季度报告以及向Securit提交的其他文件中。

*Prof. Sanjay Popat has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

*教授。Sanjay Popat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，并对其应用或使用不承担任何责任。。

1 Popat, et al. Overall Survival Among Patients Receiving Amivantamab Plus Chemotherapy vs Chemotherapy in EGFR-mutated, Advanced Non-small Cell Lung Cancer After Disease Progression on Osimertinib (MARIPOSA-2). 2024 European Society for Medical Oncology. September 14, 2024.2 Passaro P, et al. Amivantamab Plus Chemotherapy (With or Without LAZCLUZE™) vs Chemotherapy Alone in EGFR-mutated, Advanced Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib: MARIPOSA-2, a Phase 3, Global, Randomized, Controlled Trial.

1 Popat等人。在Osimertinib（MARIPOSA-2）疾病进展后，接受Amivantamab加化疗与EGFR突变的晚期非小细胞肺癌化疗的患者的总生存率。2024年欧洲肿瘤内科学会。。

2023 European Society for Medical Oncology. October 23, 2023.3 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).

2023年欧洲肿瘤内科学会。2023年10月23日。ClinicalTrials.gov。一项针对奥西替尼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的阿米万塔单抗和LAZCLUZE™联合铂类化疗与铂类化疗的研究（MARIPOSA-2）。

Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed September 2024.                4 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.5 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.9.2024© National Comprehensive Cancer Network, Inc.

网址：https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295.2024年9月访问。4 RYBREVANT®处方信息。宾夕法尼亚州霍沙姆：Janssen Biotech，Inc.5经NCCN非小细胞肺癌临床实践指南（NCCN Guidelines®）第9.2024版许可引用©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 2024.6 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA) Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04487080.

保留所有权利。要查看该指南的最新和完整版本，请在线访问NCCN.org。2024年9月访问。6 ClinicalTrials.gov。阿米万塔单抗和拉泽替尼联合治疗与奥西替尼治疗局部晚期或转移性非小细胞肺癌（MARIPOSA）的研究可在以下网址获得：https://classic.clinicaltrials.gov/ct2/show/NCT04487080.

Accessed September 2024.7 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pem.

2024年9月访问.7 ClinicalTrials.gov。与卡铂-Pem相比，阿米万塔单抗和卡铂-培美曲塞联合治疗的研究。

Media contact:Suzanne Frostsfrost@its.jnj.com

媒体联系人：苏珊娜Frostsfrost@its.jnj.com

Sarah Freemansfreem21@its.jnj.com

莎拉Freemansfreem21@its.jnj.com

Investor contact:Raychel Kruperinvestor-relations@its.jnj.com

投资者联系人：RaychelKruperinvestor-relations@its.jnj.com

U.S. Medical Inquiries +1 800 526-7736

U、 美国医疗查询+1 800 526-7736

View original content to download multimedia:https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-chemotherapy-shows-positive-overall-survival-trend-versus-chemotherapy-in-patients-with-previously-treated-egfr-mutated-lung-cancer-302248157.html

查看原始内容以下载多媒体：https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-chemotherapy-shows-positive-overall-survival-trend-versus-chemotherapy-in-patients-with-previously-treated-egfr-mutated-lung-cancer-302248157.html

SOURCE Johnson & Johnson

来源强生公司