海报库PosterKeep
PO.CT01.04 · 临床试验

Savolitinib联合Durvalumab治疗伴MET改变的EGFR野生型晚期NSCLC患者（SOUND）：一项多中心、开放标签的II期临床试验

Savolitinib combined with Durvalumab in EGFR wild-type advanced NSCLC patients with MET alterations (SOUND): A multicenter, open-label, Phase II trial

海报缩略图：Savolitinib联合Durvalumab治疗伴MET改变的EGFR野生型晚期NSCLC患者（SOUND）：一项多中心、开放标签的II期临床试验
编号 CT247 展板 12 时间 4/21 02:00–05:00 区域 Section 50 主讲 Shun Lu, MD;PhD
分会场 Phase II Clinical Trials
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作者与单位 Authors & Affiliations

Yong-Feng Yu1, Xiao-Ying Huang2, Qian Chu3, An-Wen Liu4, Li Zhuang5, Xiao-Rong Dong6, Hong-Cheng Wu7, Jian-Ying Zhou8, Shun-Dong Cang9, Yan Wang10, Yi Hu11, Zhen-Zhou Yang12, Meng-di Wu13, Xiao-yuan Wang13, Shun Lu1

1Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China,2Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China,3Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,4Department of Oncology, Nanchang University Second Affiliated Hospital, Nanchang, China,5Department of Rehabilitation and Palliative Medicine, Yunnan Cancer Hospital, Kunming, China,6Cancer Center, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China,7Ningbo Medical Centre, Li Huili Hospital affiliated of Ningbo University, Ningbo, China,8Respiratory Medicine, The First Affiliated Hospital of Zhejiang University, Department of Respiratory Disease, Hangzhou, China,9Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, China,10Research Unit of Molecular Cancer Research, Chinese Academy of Medical Sciences, Beijing, China,11Department of Oncology, The First Medical Center, Chinese PLA General Hospital, Beijing, China,12Cancer Center, The Second Affiliated Hospital of Chongqing University, Chongqing, China,13Department of Medical Affairs, AstraZeneca China, Shanghai, China

摘要 Abstract

中文摘要
背景：MET基因失调可作为NSCLC的致癌驱动因素。MET抑制剂单药治疗在伴MET改变的EGFR野生型NSCLC患者（pts）中疗效有限。临床前研究表明，MET抑制剂联合免疫治疗可协同增强抗肿瘤活性。SOUND研究旨在探索savolitinib联合durvalumab治疗伴MET改变的EGFR野生型晚期NSCLC患者的疗效与安全性。 方法：既往未接受过免疫治疗的患者根据NGS、FISH或免疫组化确定的MET改变状态，被纳入MET Ex14m队列（队列1）或MET过表达/AMP队列（队列2），接受savolitinib（600mg[体重≥50kg]/400mg[体重<50kg]，每日一次）联合durvalumab（1,500mg，每四周一次）治疗。主要终点为无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、12个月总生存（OS）率和安全性。此处，我们报告中期分析结果。 结果：截至数据截止日期（2025年1月17日），共入组47例患者并接受了至少一剂研究治疗，其中队列1（C1）24例，队列2（C2）23例。C1中，83.3%患者为腺癌，16.7%有脑转移，37.5% PD-L1≥50%，87.5%为一线治疗。C2中，56.5%为腺癌，34.8%有脑转移，56.5% PD-L1≥50%，87.0%为一线治疗。中位随访时间C1为15.4个月（m），C2为13.2个月。C1的中位PFS未达到（成熟度33.3%），C2为5.5个月（95% CI，3.2-9.2，成熟度78.3%）。研究者评估的经确认ORR在C1和C2分别为45.8%（95% CI，25.6-67.2%）和52.2%（95% CI，30.6-73.2%）。C1和C2的12个月OS率分别为82.0%和60.1%。44例（93.6%）患者观察到任何级别的治疗相关不良事件（TRAEs）。最常见的TRAEs为外周水肿（38.3%）、贫血（38.3%）、低白蛋白血症（34%）、天冬氨酸氨基转移酶升高（34%）和丙氨酸氨基转移酶（ALT）升高（31.9%）。C1中14例（58.3%）患者、C2中12例（52.2%）患者报告了3级及以上TRAEs。最常见的3级及以上TRAE为肝功能异常（14.9%）、药物性肝损伤（12.8%）和ALT升高（10.6%）。 结论：Savolitinib联合durvalumab在伴MET改变的EGFR野生型晚期NSCLC患者中显示出有前景的临床抗肿瘤活性，尤其是在伴MET ex14m的患者中。接受该联合治疗的患者应进行密切、频繁（即每周）的肝功能监测。需要更大样本量的前瞻性研究，以进一步评估该联合治疗在伴MET改变的EGFR野生型NSCLC患者中的疗效与安全性。 临床试验信息：NCT05374603
查看英文原文 English abstract
Background: Dysregulation of MET gene could serve as oncogenic driver in NSCLC. The efficacy of MET inhibitor monotherapy was limited in EGFR wild-type NSCLC patients(pts) with MET alterations. Pre-clinical study demonstrated that MET inhibitor combined with immunotherapy may synergistically enhance anti-tumor activity. SOUND study aims to explore the efficacy and safety of savolitinib plus durvalumab in EGFR wild-type advanced NSCLC pts with MET alterations. Methods: Pts who did not receive immunotherapy previously were enrolled into MET Ex14m cohort (Cohort 1) or MET Overexpression/AMP cohort (Cohort 2) according to MET alteration status determined by NGS, FISH or immunohistochemistry and received savolitinib (600mg [body weight≥50kg] / 400mg [body weight < 50kg], once daily) in combination with durvalumab (1,500 mg once every four weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), 12-month overall survival (OS) rate, and safety. Here, we report the interim analysis results. Results: At data cutoff (January 17, 2025), forty-seven pts were enrolled and received at least one dose of study treatment, with 24 in Cohort 1(C1) and 23 in Cohort 2(C2), respectively. For C1, 83.3% pts had adenocarcinoma, 16.7% had brain metastases, 37.5% had PD-L1 ≥ 50% and 87.5% were treated in first line. For C2, 56.5% had adenocarcinoma, 34.8% had brain metastases, 56.5% had PD-L1 ≥ 50% and 87.0% were treated in first line. Median follow-up was 15.4 months(m) in C1 and 13.2 m in C2. The median PFS was not reached (maturity of 33.3%) in C1 and 5.5 m (95% CI, 3.2-9.2, maturity of 78.3%) months in C2. The confirmed ORR per investigator in C1 and C2 were 45.8% (95% CI, 25.6-67.2%) and 52.2% (95% CI, 30.6-73.2%), respectively. 12-month OS rate for C1 and C2 were 82.0% and 60.1%, respectively. Any grade treatment-related adverse events (TRAEs) were observed in 44 (93.6%) pts. The most common TRAEs were peripheral oedema (38.3%), anemia (38.3%), hypoalbuminemia (34%), aspartate aminotransferase increased (34%) and alanine aminotransferase (ALT) increased (31.9%). Grade 3 and above TRAEs were reported in 14 (58.3%) pts in C1 and 12 (52.2%) pts in C2. The most common grade 3 and above TRAE were hepatic function abnormal (14.9%), drug-induced liver injury (12.8%) and ALT (10.6%) increased. Conclusions: Savolitinib plus durvalumab showed promising clinical anti-tumor activity in pts with advanced EGFR wild-type NSCLC with MET alterations, especially in pts with MET ex14m. Close and frequent(i.e. weekly) monitoring of liver function should be conducted in pts receiving this combination. Prospective studies with larger sample sizes are needed to further evaluate the efficacy and safety of this combination in EGFR wild-type NSCLC pts with MET alterations. Clinical trial information: NCT05374603
利益披露 Disclosure
Y. Yu, None.. X. Huang, None.. Q. Chu, None.. A. Liu, None.. L. Zhuang, None.. X. Dong, None.. H. Wu, None.. J. Zhou, None.. S. Cang, None.. Y. Wang, None.. Y. Hu, None.. Z. Yang, None. M. Wu, AstraZeneca Employment. X. Wang, AstraZeneca Employment. S. Lu, None.

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