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.

IF 9.6 1区医学 Q1 MEDICINE, GENERAL & INTERNAL EClinicalMedicine Pub Date : 2024-09-03 eCollection Date: 2024-09-01 DOI:10.1016/j.eclinm.2024.102791

Puyuan Xing, Shanbing Wang, Minghong Bi, Yong Liu, Jia Zeng, Xicheng Wang, Ke Xiao, Weidong Li, Jun Guo, Pu Wang, Yueyin Pan, Biyong Ren, Emei Gao, Lei Zhang, Yingchun Wang, Tianyi Gan, Guang Cheng, Yuankai Shi

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Abstract

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/m², 80 mg/m², and 100 mg/m². 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/m², 80 mg/m², and 100 mg/m² 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/m², 80 mg/m², and 100 mg/m² dose group were 33% (2/6), 33% (10/30), and 30% (9/30), respectively. The median DoR of 60 mg/m², 80 mg/m², and 100 mg/m² 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/m², 80 mg/m², and 100 mg/m² 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/m² dose group had the best benefit-risk ratio.

Funding: This study was supported by Luye Pharma Group Ltd.

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旨在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药物的疗效和安全性的 2 期剂量范围研究。

研究背景这是一项多中心、单臂、剂量范围2期研究，旨在评估不同剂量脂质体伊立替康LY01610治疗复发小细胞肺癌（SCLC）患者的疗效和安全性：该研究（NCT04381910）在全国10家医院招募了既往铂类治疗失败的复发小细胞肺癌患者。LY01610的剂量分别为60毫克/平方米、80毫克/平方米和100毫克/平方米。主要终点为研究者评估的客观反应率（ORR）和研究者评估的反应持续时间（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：2020年9月3日至2022年3月3日，共有66名患者入组，其中6人、30人和30人分别被分配到60 mg/m2、80 mg/m2和100 mg/m2剂量组，无化疗间隔2、80 mg/m2和100 mg/m2剂量组分别为68%（45/66）、33%（2/6）、33%（10/30）和30%（9/30）。60毫克/平方米、80毫克/平方米和100毫克/平方米剂量组的中位DoR分别为4.2个月（95% CI，2.8-未达到）、6.9个月（95% CI，2.5-9.9）和4.0个月（95% CI，2.7-6.8）。60毫克/平方米、80毫克/平方米和100毫克/平方米剂量组的≥3级治疗相关不良事件（TRAE）发生率分别为33%（2/6）、47%（14/30）和50%（15/30）。在所有66例患者中，最常见的≥3级TRAE为中性粒细胞减少（27%）、白细胞减少（24%）和贫血（15%）：LY01610对复发SCLC患者具有良好的临床疗效和可控的安全性，80 mg/m2剂量组的获益风险比最佳：本研究得到了绿叶制药集团有限公司的支持。

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来源期刊

EClinicalMedicine Medicine-Medicine (all)

CiteScore

18.90

自引率

1.30%

发文量

506

审稿时长

22 days

期刊介绍： eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.