Application based on Phase 3 PALOMA-3 results showing five-fold reduction in infusion-related reactions with five-minute administration of subcutaneous amivantamab

基于3期PALOMA-3结果的应用显示，皮下注射阿米万塔单抗5分钟后，输注相关反应减少了5倍

Longer overall survival, progression-free survival and duration of response also observed with subcutaneous amivantamab

皮下阿米万塔单抗也可观察到更长的总生存期，无进展生存期和反应持续时间

RARATIN, N.J., June 17, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) announced today the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) for all currently approved or submitted indications of intravenous (IV) RYBREVANT® (amivantamab-vmjw) in certain patients with non-small cell lung cancer (NSCLC)..

新泽西州拉拉廷，2024年6月17日/新闻专线/--强生公司（纽约证券交易所：JNJ）今天宣布，向美国食品和药物管理局（FDA）提交生物制剂许可证申请（BLA），用于将阿米万塔单抗和重组人透明质酸酶固定组合用于皮下给药（SC amivantamab），用于某些非小细胞肺癌（NSCLC）患者目前批准或提交的所有静脉注射（IV）RYBREVANT®（amivantamab vmjw）适应症。。

Data from the Phase 3 PALOMA-3 study (NCT05388669) presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology showed SC amivantamab had comparable overall response rates to IV administration in patients with NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or L858R mutations.

2024年美国临床肿瘤学会（ASCO）年会上发表的第3期PALOMA-3研究（NCT05388669）的数据并发表在《临床肿瘤学杂志》上，显示SC阿米万塔单抗对具有表皮生长因子受体（EGFR）外显子19缺失或L858R突变的NSCLC患者静脉注射的总体反应率相当。

SC amivantamab also demonstrated significantly shorter administration time and a five-fold reduction in infusion-related reactions, alongside longer overall survival, progression-free survival and duration of response.1 Efficacy results like these have not been seen before in a study assessing IV and SC comparability.

SC-amivantamab还显示出显着缩短的给药时间和输注相关反应的五倍减少，以及更长的总生存期，无进展生存期和反应持续时间。在评估IV和SC可比性的研究中，以前从未见过类似的疗效结果。

The BLA submission includes data from the Phase 2 PALOMA-2 (NCT05498428) study evaluating SC amivantamab in settings where IV amivantamab has been previously submitted for approval and is intended to support dosing schedules of every two and every three weeks.2 .

BLA提交的数据包括来自第二阶段PALOMA-2（NCT05498428）研究的数据，该研究评估了先前已提交IV amivantamab供批准的环境中的SC amivantamab，旨在支持每两周和每三周的给药时间表。

'RYBREVANT administered intravenously is a foundational treatment for patients with EGFR-mutated NSCLC,' said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. 'This subcutaneous option, administered in approximately five minutes, is a clinically important advancement that could transform the treatment experience for patients, oncologists and nursing staff.

强生创新医学公司实体瘤临床开发副总裁Kiran Patel医学博士说，静脉注射瑞勃万特是EGFR突变NSCLC患者的基础治疗方法。

We look forward to working with the FDA and global regulators in the review of these applications.'.

我们期待着与FDA和全球监管机构合作审查这些申请。”。

Today's submission follows two recent milestones for the RYBREVANT® IV formulation, including the approval of RYBREVANT® in combination with chemotherapy as the first FDA-approved therapy for first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations supported by the Phase 3 PAPILLON study and a CHMP positive opinion for RYBREVANT® in combination with chemotherapy for this indication in Europe..

今天的提交遵循了RYBREVANT®IV制剂最近的两个里程碑，包括批准RYBREVANT®联合化疗作为FDA批准的第一种治疗EGFR外显子20插入突变的NSCLC患者的一线治疗方法，该治疗方法得到了3期PAPILLON研究的支持，以及CHMP对RYBREVANT®联合化疗在欧洲的积极意见。。

About PALOMA-3

关于PALOMA-3

PALOMA-3 (NCT05388669), which enrolled 418 patients, is a randomized, open-label Phase 3 study evaluating the pharmacokinetics (PK), efficacy and safety of subcutaneous amivantamab (administered via manual injection) combined with lazertinib compared to IV amivantamab and lazertinib in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and chemotherapy.

PALOMA-3（NCT05388669）招募了418名患者，是一项随机，开放标签的3期研究，评估皮下阿米万塔单抗（通过手动注射给药）联合拉泽替尼的药代动力学（PK），疗效和安全性，与静脉注射阿米万塔单抗和拉泽替尼相比，在奥西替尼和化疗进展后EGFR突变的晚期或转移性NSCLC患者中。

The co-primary PK endpoints of the study were trough concentration (Ctrough on Cycle [C] 2 Day [D] 1 or C4D1) and C2 area under the curve (AUCD1-D15). Key secondary endpoints were objective response rate and progression-free survival. Overall survival was a predefined exploratory endpoint. Prophylactic anticoagulation was recommended for the first four months of treatment.1 .

该研究的共同主要PK终点是谷浓度（Ctrough on Cycle[C]2 Day[D]1或C4D1）和曲线下C2面积（AUCD1-D15）。关键的次要终点是客观缓解率和无进展生存期。总生存率是一个预定义的探索终点。建议在治疗的前四个月进行预防性抗凝治疗。

About the PALOMA-2 Study

关于PALOMA-2研究

PALOMA-2 (NCT05498428) is an open-label Phase 2 study evaluating the efficacy, safety, and PK of first-line SC amivantamab (administered via manual injection) combined with lazertinib and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC. Sixty-eight and 58 patients were enrolled in Cohorts 1 and 6, respectively.

PALOMA-2（NCT05498428）是一项开放标签的2期研究，评估一线SC阿米万塔单抗（通过手动注射给药）联合拉泽替尼和/或化疗对EGFR突变的晚期或转移性NSCLC患者的疗效，安全性和PK。第1组和第6组分别招募了68名和58名患者。

Prophylactic anticoagulation for the first four months of treatment was recommended in Cohort 1 and mandatory in Cohort 6. The primary endpoint was objective response rate (ORR) as assessed by the investigator per RECIST v1.1.2.

队列1建议在治疗的前四个月进行预防性抗凝治疗，队列6则强制进行预防性抗凝治疗。主要终点是研究者根据RECIST v1.1.2评估的客观缓解率（ORR）。

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.3 In the subcutaneous formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology..

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，通过FDA批准的测试检测，其疾病在铂类化疗时或之后进展。3在皮下制剂中，阿米万塔单抗与重组人透明质酸酶PH20（rHuPH20），Halozyme的ENHANZE®药物递送技术共同配制。。

RYBREVANT® is also approved in the U.S. 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. In October 2023, a type II extension of indication application was submitted to the European Medicines Agency (EMA) seeking approval of RYBREVANT® for this indication..

RYBREVANT®在美国也被批准与化疗（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。2023年10月，向欧洲药品管理局（EMA）提交了II型适应症延期申请，寻求RYBREVANT®对该适应症的批准。。

In December 2023, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) together with a New Drug Application (NDA) to the U.S. FDA for RYBREVANT® in combination with 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.

2023年12月，强生公司向美国FDA提交了补充生物制剂许可证申请（sBLA）和新药申请（NDA），用于RYBREVANT®联合拉泽替尼治疗成人局部晚期或转移性非小细胞肺癌EGFR外显子19缺失或L858R替代突变患者的一线治疗，如FDA批准的测试所检测。

This submission is based on the Phase 3 MARIPOSA study and was granted Priority Review in February 2024. A marketing authorization application (MAA) and type II extension of indication application were also submitted to the EMA seeking approval of lazertinib in combination with RYBREVANT® based on the MARIPOSA study..

该提交基于第3阶段MARIPOSA研究，并于2024年2月获得优先审查。营销授权申请（MAA）和II型适应症扩展申请也已提交给EMA，寻求根据MARIPOSA研究批准拉泽替尼与RYBREVANT®联合使用。。

In November 2023, Johnson & Johnson submitted an 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. A type II extension of indication application was also submitted to the EMA seeking approval of RYBREVANT® for this indication..

2023年11月，强生公司向美国FDA提交了一份sBLA，要求RYBREVANT®联合化疗治疗EGFR突变的NSCLC患者，这些患者根据MARIPOSA-2研究在osimertinib上或之后进展。还向EMA提交了II型适应症扩展申请，寻求RYBREVANT®对该适应症的批准。。

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 carboplatin and pemetrexed as a preferred (Category 1 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.4 †‡  .

Amivantamab vmjw（RYBREVANT®）联合卡铂和培美曲塞作为初治的初治晚期或转移性EGFR外显子20插入突变阳性晚期NSCLC患者的首选（1类推荐）一线治疗，或作为后续治疗选择（2A类推荐）对于铂类化疗或铂类化疗后有或无免疫治疗进展且EGFR外显子20插入突变阳性晚期NSCLC的患者。

Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a preferred (Category 1 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.4 †‡

Amivantamab vmjw（RYBREVANT®）加化疗作为局部晚期或转移性NCSLC患者EGFR外显子19缺失或外显子21 L858R突变的首选（1类推荐）后续治疗，这些患者在接受osimertinib治疗后出现疾病进展。4†‡

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.4 †‡

Amivantamab vmjw（RYBREVANT®）作为后续治疗选择（2A类推荐），用于铂类化疗后或铂类化疗后有或无免疫治疗进展且EGFR外显子20插入突变阳性NSCLC的患者。4†‡

RYBREVANT® is being studied in multiple clinical trials in NSCLC, including:

RYBREVANT®正在NSCLC的多项临床试验中进行研究，包括：

The 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.5

第一阶段PALOMA（NCT04606381）研究评估了基于安全性和药代动力学的皮下注射阿米万塔单抗的可行性，并确定了阿米万塔单抗皮下给药的剂量，剂量方案和制剂

The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.2

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

The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.1

3期PALOMA-3（NCT05388669）研究评估了拉泽替尼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。1

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.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

The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT® (with or without lazertinib) 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.7  .

3期MARIPOSA-2（NCT04988295）研究评估了在osimertinib或osimertinib后疾病进展后局部晚期或转移性EGFR ex19del或L858R替代NSCLC患者中RYBREVANT®（有或没有拉泽替尼）和卡铂-培美曲塞与卡铂-培美曲塞单独治疗的疗效。

The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT® in combination with lazertinib versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.8

3期MARIPOSA（NCT04487080）研究评估了RYBREVANT®联合拉泽替尼与osimertinib和单独拉泽替尼治疗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

The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT® in patients with advanced NSCLC.9

1期蛹（NCT02609776）研究评估晚期非小细胞肺癌患者的RYBREVANT®9

The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT® in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.10

1/1b期CHRYSALIS-2（NCT04077463）研究评估了RYBREVANT®联合拉泽替尼和拉泽替尼作为EGFR突变晚期NSCLC患者的单一疗法

The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT® and capmatinib combination therapy in locally advanced or metastatic NSCLC.11

1/2期METalmark（NCT05488314）研究评估RYBREVANT®和capmatinib联合治疗局部晚期或转移性NSCLC.11

The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.12

1/2期PolyDamas（NCT05908734）研究评估RYBREVANT®和cetrelimab联合治疗局部晚期或转移性NSCLC.12

The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT® in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.13

2期SKIPPirr研究（NCT05663866）探讨了如何降低RYBREVANT®联合拉泽替尼治疗复发或难治性EGFR突变的晚期或转移性NSCLC的首次剂量输注相关反应的发生率和/或严重程度

For more information, visit: https://www.RYBREVANT.com.

有关更多信息，请访问：https://www.RYBREVANT.com.

About Lazertinib

关于Lazertinib

Lazertinib is an oral, third-generation, brain-penetrant EGFR tyrosine kinase inhibitor (TKI) that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. An analysis of the efficacy and safety of lazertinib from the Phase 3 study was published in The Journal of Clinical Oncology in 2023.

拉泽替尼是一种口服的第三代脑渗透性EGFR酪氨酸激酶抑制剂（TKI），可靶向T790M突变和激活EGFR突变，同时保留野生型EGFR。2023年，《临床肿瘤学杂志》发表了对拉泽替尼3期研究的疗效和安全性的分析。

In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.14.

2018年，Janssen Biotech，Inc.与Yuhan Corporation签订了lazertinib.14开发许可证和合作协议。

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.15,16 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.17 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.18 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.17, 18, 19, 20, 21, 22 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.23 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.24, 25 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.26 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.27.

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%。15,16 NSCLC的主要亚型是腺癌，鳞状细胞癌和大细胞癌。17 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。18 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。17、18、19、20、21、22 EGFR ex19del或EGFR L858R突变是最常见的EGFR突变。23所有接受EGFR酪氨酸激酶抑制剂（TKIs）治疗的晚期NSCLC和EGFR突变患者均不到20%。24、25个EGFR外显子20插入突变是第三大最常见的激活EGFR突变。26个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%。

RYBREVANT® IMPORTANT SAFETY INFORMATION3

RYBREVANT®重要安全信息3

WARNINGS AND PRECAUTIONS

警告和注意事项

The safety population of RYBREVANT® with carboplatin and pemetrexed described in Warnings and Precautions was based on 151 patients in the PAPILLON study.

警告和注意事项中描述的RYBREVANT®与卡铂和培美曲塞的安全人群是基于PAPILLON研究中的151名患者。

The safety population of RYBREVANT® as a single agent described in Warnings and Precautions was based on 129 patients in the CHRYSALIS study.

警告和注意事项中描述的RYBREVANT®作为单一药物的安全人群是基于蛹研究中的129名患者。

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.

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。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

RYBREVANT® in combination with carboplatin and pemetrexed can cause infusion-related reactions. Based on the safety population, 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®..

RYBREVANT®联合卡铂和培美曲塞可引起输注相关反应。根据安全人群，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

Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT® as a single agent. 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.

根据安全人群，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%。

Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. 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..

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。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. Monitor patients for any 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任何体征和症状。

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

。根据严重程度降低输液速度或永久停用RYBREVANT®。。

Interstitial Lung Disease/Pneumonitis

间质性肺病/肺炎

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

RYBREVANT®可引起间质性肺病（ILD）/肺炎。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

Based on the safety population, Grade 3 ILD/pneumonitis occurred in 2.6% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed. All patients required permanent discontinuation.

根据安全人群，RYBREVANT®联合卡铂和培美曲塞治疗的患者中有2.6%发生3级ILD/肺炎。所有患者都需要永久停药。

RYBREVANT® as a Single Agent

RYBREVANT®作为单一代理

Based on the safety population, 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.

根据安全人群，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). Immediately withhold RYBREVANT® 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）。对于疑似ILD/肺炎的患者，立即停用RYBREVANT®，如果确诊ILD/肺炎，则永久停用。

Dermatologic Adverse Reactions

皮肤科不良反应

RYBREVANT® can cause rash (including dermatitis acneiform), pruritus, and dry skin.

RYBREVANT®可引起皮疹（包括痤疮样皮炎）、瘙痒和皮肤干燥。

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

RYBREVANT® in combination with carboplatin and pemetrexed can cause dermatologic adverse reactions. Based on the safety population, 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..

RYBREVANT®联合卡铂和培美曲塞可引起皮肤病不良反应。。19%的患者出现皮疹导致剂量减少；2%永久停用RYBREVANT®，1.3%停用培美曲塞。。

RYBREVANT® as a Single Agent

RYBREVANT®作为单一代理

Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT®, 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. .

根据安全人群，74%接受RYBREVANT®治疗的患者出现皮疹，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.

。

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT®. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free emollient cream is recommended for dry skin.

指导患者在使用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的润肤霜。

If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. 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.

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。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。

Withhold, dose reduce, or permanently discontinue RYBREVANT® based on severity. .

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, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis.

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

RYBREVANT® with Carboplatin and Pemetrexed

含卡铂和培美曲塞的RYBREVANT®

Based on the safety population, RYBREVANT® in combination with carboplatin and pemetrexed can cause ocular toxicity including blepharitis, dry eye, conjunctival redness, blurred vision, and eye pruritus. All events were Grade 1-2.

根据安全人群，RYBREVANT®联合卡铂和培美曲塞可引起眼部毒性，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

Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT®. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce, or permanently discontinue RYBREVANT® based on severity. .

根据安全人群，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。立即将出现眼部症状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® can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT®..

根据其作用机制和动物模型的发现，RYBREVANT®给孕妇服用时会造成胎儿伤害。告知女性生殖潜力对胎儿的潜在风险。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。。

Adverse Reactions

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。7名患者（4.6%）因肺炎，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而发生致命不良反应。。

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。。

Please read full Prescribing Information for RYBREVANT®.

请阅读RYBREVANT®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

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 lazertinib. The reader is cautioned not to rely on these forward-looking statements.

。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.and/or Johnson & Johnson.

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出现已知或未知的风险或不确定性，实际结果可能与Janssen Research＆Development，LLC，Janssen Biotech，Inc.和/或Johnson＆Johnson的预期和预测有很大差异。

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.

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；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；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 Securities and Excha.

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证券和交易所提交的其他文件中。

†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.

。

§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。。

1 ClinicalTrials.gov. A Study of Lazertinib 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 May 2024.2 ClinicalTrials.gov.

1 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，拉泽替尼与皮下阿米万塔单抗相比静脉注射阿米万塔单抗的研究。https://clinicaltrials.gov/ct2/show/NCT05388669.2024年5月访问.2 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 May 2024.3 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.4 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.

阿米万塔单抗在晚期或转移性实体瘤患者中的研究，包括表皮生长因子受体（EGFR）突变的非小细胞肺癌（PALOMA-2）。https://clinicaltrials.gov/ct2/show/NCT05498428.2024年5月访问。RYBREVANT®处方信息。宾夕法尼亚州霍沙姆：Janssen Biotech，Inc.4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。

All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed M 2024.5 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/study/NCT04606381.

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。访问M 2024.5 ClinicalTrials.gov。这是一项关于阿米万塔单抗皮下（SC）给药治疗晚期实体恶性肿瘤（PALOMA）的研究。网址：https://clinicaltrials.gov/study/NCT04606381.

Accessed May 2024.6 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).

2024年5月访问.6 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。

Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed May 2024.7 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib 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.

网址：https://clinicaltrials.gov/ct2/show/NCT04538664.2024年5月访问.7 ClinicalTrials.gov。对表皮生长因子受体（EGFR）突变的局部晚期或转移性非小细胞肺癌患者，阿米万塔单抗和拉泽替尼联合铂类化疗与铂类化疗相比的研究。

Media contact:Suzanne Frost+1 416-317-0304   Sarah Freeman +1 215-510-4758

媒体联系人：苏珊·弗罗斯特+1 416-317-0304莎拉·弗里曼+1 215-510-4758

Investor contact:Raychel Kruperinvestor-relations@its.jnj.com  U.S. Medical Inquiries  +1 800 526-7736

投资者联系人：RaychelKruperinvestor-relations@its.jnj.com美国医疗查询+1 800 526-7736

SOURCE Johnson & Johnson

来源强生公司