恩考芬尼联合比美替尼治疗中国BRAFV600E突变转移性非小细胞肺癌患者的II期研究：OCEAN II研究结果
A phase 2 study of encorafenib in combination with binimetinib for Chinese participants with BRAFV600E mutated metastatic non-small cell lung cancer: Results from the OCEAN II study.
作者
作者单位
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: zhouhq@sysucc.org.cn.
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address: gzzhouqing@126.com.
- Shandong Cancer Hospital, Huaiyin District, Jinan, Shandong Province, China. Electronic address: guoqs369@163.com.
- Shanxi Cancer Hospital, China. Electronic address: guowei812@126.com.
- Harbin Medical University Cancer Hospital, Heilongjiang, China. Electronic address: Gongyanchen0123@163.com.
- Beijing Chest Hospital, Capital Medical University, China. Electronic address: lza@vip.163.com.
- Zhejiang Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China. Electronic address: fanyun@zjcc.org.cn.
- Chongqing Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, China. Electronic address: pipili@sina.com.
- Clinical Research Center and Chest Department, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. Electronic address: ymchen@vghtpe.gov.tw.
- Pierre Fabre Laboratories, France. Electronic address: kenza.bouras@pierre-fabre.com.
- Pierre Fabre Laboratories, France. Electronic address: laurence.del.frari@pierre-fabre.com.
- Pierre Fabre Laboratories, China. Electronic address: angela.guo@pierre-fabre.com.
- Pierre Fabre Laboratories, France. Electronic address: Isabelle.klauck@pierre-fabre.com.
- Pierre Fabre Laboratories, France. Electronic address: benoit.sansas@pierre-fabre.com.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: zhangli@sysucc.org.cn.
摘要
中文
正在进行的OCEAN II研究（ClinicalTrials.gov标识符：NCT05195632）评估了恩考芬尼联合比美替尼（E+B）在中国BRAFV600E突变转移性非小细胞肺癌（NSCLC）患者中的疗效。纳入患有转移性不可切除的IV期BRAFV600E突变NSCLC（未接受过治疗或既往接受过不包括BRAF/MEK抑制剂在内的全身治疗）的参与者，进行了一项分为两部分（安全性导入期[SLI]和关键部分[PP]）的II期研究。参与者每日口服恩考芬尼（450mg）和每日两次口服比美替尼（总剂量90mg）。主要终点是SLI期间的剂量限制性毒性（DLT）和PP期间经独立中央审查确认的客观缓解率（cORR-ICR）。次要终点是其他疗效、安全性和药代动力学指标。共入组63名参与者。SLI期间发生1例DLT（非严重的3级脂肪酶升高），被认为可能与E+B相关，但未经干预即缓解，支持启动PP。前50名参与者的预设统计学疗效标准已达到。在主要分析中，cORR-ICR为59%（95%CI 45-72）。在后期的事后分析中，cORR-ICR为61%（95%CI 47-74），疾病控制率为87%（95%CI 75-95）。中位时间（95%CI）分别为：至缓解时间1.8个月，缓解持续时间17.5个月，无进展生存期13.8个月（7.5-不可估计），总生存期27.9个月（14.7-30.0）。98.4%的参与者经历了至少1次治疗相关TEAE，55.6%出现任何3级及以上TEAE。9名（14.3%）参与者因不良事件停用任何药物。这些数据证实了E+B对中国BRAFV600E突变转移性NSCLC患者的临床获益，该人群具有独特的基因组和疾病特征。在中国参与者中未发现新的安全性问题。
English
The ongoing OCEAN II study (ClinicalTrials.gov identifier: NCT05195632) evaluates encorafenib in combination with binimetinib (E+B) in Chinese participants with BRAFV600E-mutated metastatic non-small cell lung cancer (NSCLC). Participants with metastatic unresectable stage IV BRAFV600E-mutated NSCLC (treatment-naïve or with prior systemic therapy excluding BRAF/MEK-inhibitors), were enrolled in a phase 2 study with two parts: safety lead-in (SLI) and pivotal part (PP). Participants received daily oral encorafenib (450mg) and twice daily oral binimetinib (90mg total). Primary endpoints were dose-limiting toxicities (DLT) during SLI and confirmed objective response rate by independent central review (cORR-ICR) during PP. Secondary endpoints were other measures of efficacy, safety, and pharmacokinetics. In total, 63 participants were enrolled. One DLT (non-serious Grade 3 lipase increased) during SLI considered possibly related to E+B resolved without intervention, supporting initiation of PP. Pre-defined statistical efficacy criteria on the first 50 participants were met. In the main analysis, cORR-ICRwas59% (95%CI 45-72). At a later ad hoc analysis, cORR-ICR was 61% (95%CI 47-74), disease control rate 87% (95%CI 75-95). Medians (95%CI) were, time-to-response 1.8 months, duration of response 17.5 months, progression-free survival 13.8 months (7.5-not estimable), overall survival 27.9 months (14.7-30.0). 98.4% of participants experienced ≥1 treatment-related TEAE, and 55.6% had any Grade ≥3 TEAE. Nine (14.3%) participants discontinued any drug due to adverse events. These data confirm the clinical benefit of E+B in Chinese participants with BRAFV600E-mNSCLC, a population with distinct genomic and disease characteristics. No new safety concerns were identified in Chinese participants.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区