FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations
正文 · 中文译文
FDA批准amivantamab-vmjw联合卡铂和培美曲塞用于携带EGFR外显子19缺失或L858R突变的非小细胞肺癌 癌症批准 肿瘤学（癌症）/血液系统恶性肿瘤批准通知 进行中 | 癌症加速批准 已证实临床获益 | 癌症加速批准 已撤回 | 癌症加速批准 其他 | 癌症加速批准 2024年9月19日，美国食品药品监督管理局（FDA）批准amivantamab-vmjw（Rybrevant，Janssen Biotech， Inc.）联合卡铂和培美曲塞，用于治疗携带表皮生长因子受体（EGFR）外显子19缺失或外显子21 L858R置换突变的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者，且其疾病在EGFR酪氨酸激酶抑制剂治疗期间或之后出现进展。 Rybrevant的完整处方信息将发布在Drugs@FDA上。 疗效与安全性 疗效在MARIPOSA-2（NCT04988295）中进行了评价，该研究是一项随机、开放标签、多中心试验，纳入657例携带EGFR外显子19缺失或外显子21 L858R置换突变且在接受奥希替尼期间或之后出现疾病进展的局部晚期或转移性NSCLC患者。患者按（1:2:2）随机接受amivantamab-vmjw联合卡铂和培美曲塞（amivantamab + CP）、卡铂和培美曲塞（CP），或amivantamab-vmjw作为另一联合方案的一部分。 主要疗效结局指标为盲态独立中心审查（BICR）评估的无进展生存期（PFS），用于比较阿米万他单抗+CP与CP。根据BICR评估的客观缓解率（ORR）和总生存期（OS）为关键次要结局指标。阿米万他单抗+CP组的中位PFS为6.3个月（95% CI：5.6，8.4），CP组为4.2个月（95% CI：4.0，4.4）（风险比0.48 [95% CI：0.36，0.64]，p值<0.0001）。阿米万他单抗+CP组确认的ORR为53%（95% CI：44，62），CP组为29%（95% CI：23，35）（p值<0.0001）。 在预设的OS第二次期中分析时，已发生最终分析所需死亡事件的85%，OS差异无统计学意义。分层OS风险比为0.73（95% CI：0.54，0.99）。 最常见的不良反应（≥20%）为皮疹、输注相关反应、疲乏、甲毒性、恶心、便秘、水肿、口腔炎、食欲减退、肌肉骨骼疼痛、呕吐和COVID-19感染。 阿米万他单抗-vmjw的推荐剂量基于基线体重。具体剂量信息参见处方信息。 本综述是在Project Orbis框架下开展的，该项目是美国食品药品监督管理局（FDA）肿瘤卓越中心的一项倡议。Project Orbis为国际合作伙伴之间肿瘤药物的同步提交和审评提供了一个框架。本次审评中，FDA与澳大利亚治疗用品管理局（TGA）、巴西卫生监管局（ANVISA）和加拿大卫生部进行了合作。其他监管机构的申请审评正在进行中。 快速通道项目 本次审评使用了评估辅助工具（Assessment Aid），这是申请人自愿提交的材料，用以协助FDA的评估。申请人自愿提交的材料，用以协助FDA的评估。 医疗专业人员应将所有怀疑与使用任何药物和器械相关的严重不良事件报告至FDA的MedWatch报告系统，或致电1-800-FDA-1088。 如需获取研究性肿瘤产品单患者IND方面的协助，医疗专业人员可联系OCE的Project Facilitate，电话240-402-0004，或发送电子邮件至OncProjectFacilitate@fda.hhs.gov。 在X上关注肿瘤卓越中心：@FDAOncology。 内容更新日期： 2024年9月19日 受监管产品 药物 肿瘤学
正文 · 英文原文
FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations Cancer Approvals Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals On September 19, 2024, the Food and Drug Administration approved amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) with carboplatin and pemetrexed for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor. Full prescribing information for Rybrevant will be posted on Drugs@FDA. Efficacy and Safety Efficacy was evaluated in MARIPOSA-2 (NCT04988295), a randomized, open-label, multicenter trial in 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib. Patients were randomized (1:2:2) to receive amivantamab-vmjw with carboplatin and pemetrexed (amivantamab + CP), carboplatin and pemetrexed (CP), or amivantamab-vmjw as part of another combination regimen. The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) for the comparison between amivantamab + CP and CP. Overall response rate (ORR) per BICR and overall survival (OS) were key secondary outcome measures. Median PFS was 6.3 months (95% CI: 5.6, 8.4) in the amivantamab + CP arm and 4.2 months (95% CI: 4.0, 4.4) in the CP arm (hazard ratio 0.48 [95% CI: 0.36, 0.64], p-value<0.0001). The confirmed ORR was 53% (95% CI: 44, 62) in the amivantamab + CP arm and 29% (95% CI: 23, 35) in the CP arm (p-value<0.0001). At the prespecified second interim analysis of OS, with 85% of the deaths needed for the final analysis, there was no statistically significant difference in OS. The stratified OS hazard ratio was 0.73 (95% CI: 0.54, 0.99). The most common adverse reactions (≥20%) were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection. The recommended amivantamab-vmjw dose is based on baseline body weight. See the prescribing information for specific dosage information. This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), and Health Canada. The application reviews are ongoing at the other regulatory agencies. Expedited Programs This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. submission from the applicant to facilitate the FDA’s assessment. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. Follow the Oncology Center of Excellence on X: @FDAOncology. Content current as of: 09/19/2024 Regulated Product(s) Drugs Oncology
摘要 待译
On September 19, 2024, the FDA approved amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) with carboplatin and pemetrexed for adult patients with locally advanced or metastatic non-small cell lung cancer.