评估脂质体伊立替康（LY01610）作为复发小细胞肺癌患者二线治疗的疗效和安全性的2期剂量范围研究。
Phase 2 dose-ranging study to evaluate the efficacy and safety of liposomal irinotecan (LY01610) as a second-line treatment for patients with relapsed small cell lung cancer.
作者信息
Xing Puyuan, Wang Shanbing, Bi Minghong, Liu Yong, Zeng Jia, Wang Xicheng, Xiao Ke, Li Weidong, Guo Jun, Wang Pu, Pan Yueyin, Ren Biyong, Gao Emei, Zhang Lei, Wang Yingchun, Gan Tianyi, Cheng Guang, Shi Yuankai
机构信息
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, P.R. China.
Department of Oncology, Yibin Second People's Hospital, Yibin, Sichuan, 644000, P.R. China.
出版信息
EClinicalMedicine. 2024 Sep 3;75:102791. doi: 10.1016/j.eclinm.2024.102791. eCollection 2024 Sep.
BACKGROUND
This was a multicenter, single-arm dose-ranging phase 2 study aimed to assess the efficacy and safety of LY01610, a liposomal irinotecan, at various doses for patients with relapsed small cell lung cancer (SCLC).
METHODS
This study (NCT04381910) enrolled patients with relapsed SCLC at 10 hospitals across China, who have failed with previous platinum-based treatments. LY01610 was administered at doses of 60 mg/m, 80 mg/m, and 100 mg/m. Primary endpoints were investigator-assessed objective response rate (ORR) and investigator-assessed duration of response (DoR). Secondary endpoints included investigator-assessed disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS), and safety.
FINDINGS
From September 3, 2020 to March 3, 2022, a total of 66 patients were enrolled, with 6, 30, and 30 allocated to the 60 mg/m, 80 mg/m, and 100 mg/m dose groups, respectively, with 68% (45/66) having a chemotherapy-free interval <90 days. In all 66 patients, the ORR was 32% (21/66, 95% confidence interval [CI], 21-44), with a median DoR of 5.2 months (95% CI, 3.0-8.3). Median PFS and OS were 4.0 (95% CI, 2.9-5.5) and 9.7 (95% CI, 7.2-12.3) months, respectively. The ORR of 60 mg/m, 80 mg/m, and 100 mg/m dose group were 33% (2/6), 33% (10/30), and 30% (9/30), respectively. The median DoR of 60 mg/m, 80 mg/m, and 100 mg/m dose group were 4.2 (95% CI, 2.8-not reached), 6.9 (95% CI, 2.5-9.9), and 4.0 (95% CI, 2.7-6.8) months, respectively. The incidence of ≥ grade 3 treatment-related adverse events (TRAEs) in the 60 mg/m, 80 mg/m, and 100 mg/m dose group were 33% (2/6), 47% (14/30), and 50% (15/30), respectively. The most common ≥ grade 3 TRAEs of all 66 patients were neutropenia (27%), leukopenia (24%) and anemia (15%).
INTERPRETATION
LY01610 exhibited promising clinical efficacy and manageable safety profiles in patients with relapsed SCLC, the 80 mg/m dose group had the best benefit-risk ratio.
FUNDING
This study was supported by Luye Pharma Group Ltd.
背景
这是一项多中心、单臂剂量范围探索性2期研究，旨在评估脂质体伊立替康LY01610在不同剂量下对复发小细胞肺癌（SCLC）患者的疗效和安全性。
方法
本研究（NCT04381910）在中国10家医院招募复发SCLC患者，这些患者既往铂类治疗失败。LY01610的给药剂量分别为60mg/m²、80mg/m²和100mg/m²。主要终点为研究者评估的客观缓解率（ORR）和研究者评估的缓解持续时间（DoR）。次要终点包括研究者评估的疾病控制率（DCR）、研究者评估的无进展生存期（PFS）、总生存期（OS）和安全性。
结果
从2020年9月3日至2022年3月3日，共纳入66例患者，分别有6例、30例和30例被分配至60mg/m²、80mg/m²和100mg/m²剂量组，68%（45/66）的患者化疗间隔<90天。在所有66例患者中，ORR为32%（21/66，95%置信区间[CI]，21-44），中位DoR为5.2个月（95%CI，3.0-8.3）。中位PFS和OS分别为4.0（95%CI，2.9-5.5）和9.7（95%CI，7.2-12.3）个月。60mg/m²、80mg/m²和100mg/m²剂量组的ORR分别为33%（2/6）、33%（10/30）和30%（9/30）。60mg/m²、80mg/m²和100mg/m²剂量组的中位DoR分别为4.2（95%CI，2.8-未达到）、6.9（95%CI，2.5-9.9）和4.0（95%CI，2.7-6.8）个月。60mg/m²、80mg/m²和100mg/m²剂量组≥3级治疗相关不良事件（TRAEs）的发生率分别为33%（2/6）、47%（14/30）和50%（15/30）。所有66例患者中最常见的≥3级TRAEs为中性粒细胞减少（27%）、白细胞减少（24%）和贫血（15%）。
解读
LY01610在复发SCLC患者中显示出有前景的临床疗效和可管理的安全性，80mg/m²剂量组具有最佳的获益风险比。
资助
本研究由绿叶制药集团有限公司资助。
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