一项pembrolizumab联合plinabulin和docetaxel治疗转移性非小细胞肺癌和进展性疾病（PD）患者的2期研究，这些患者在单独免疫治疗（抗PD-1/PD- l1抑制剂）或联合铂双药化疗后接受治疗

IF 7.6 1区医学 Q1 HEALTH CARE SCIENCES & SERVICES

The Lancet Regional Health: Western Pacific Pub Date : 2025-02-01 DOI:10.1016/j.lanwpc.2024.101306

Yan Xu, Xiaoxing Gao, Minjiang Chen, Xiaoyan Liu, Jing Zhao, Wei Zhong, Mengzhao Wang

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引用次数: 0

摘要

基于免疫检查点抑制剂（ICI）的治疗方案已经成为一线非小细胞肺癌治疗的标准护理方案。一旦进展，不建议继续使用ICI单药治疗，化疗的疗效有限（ORR ~ 10%与doc），因此有很高的未满足临床需求。Plin是一种选择性免疫调节微管结合剂，可促进树突状细胞成熟，增强抗肿瘤T细胞反应，作为一种与pemb和doc联合使用的新方案，具有克服免疫治疗耐药性的潜力。这项2期研究旨在评估pemb + plin和doc在ICI后进展的转移性NSCLC患者中的疗效和安全性。方法在这项研究者发起的单臂、开放标签、2期试验中，纳入了在ICI治疗后获得耐药的转移性NSCLC患者（临床试验信息：NCT05599789）。参与者静脉注射pemb 200 mg D1， plin 30 mg/m2 D1和doc 75 mg/m2 D1，周期21天。主要终点是RECIST 1.1中基于研究者的ORR。次要终点包括PFS、OS、DoR和毒性。OS、PFS、DOR分析采用Kaplan-Meier法。该研究计划招募47名患者，并对其中19名患者进行正式的中期分析。截至2024年10月10日数据截止，38名患者入组，35名可评估的ITT人群进行了分析。中位随访时间为8.8个月(M)，中位年龄为68.0岁（50-83岁），男性77.1%，女性22.9%。65.7%的人现在或曾经吸烟。组织学上60%为非鳞状细胞癌，40%为鳞状细胞癌。确诊ORR为18.2%。DCR为89.7%(定义为PR和SD >；4 M)， DoR中位数为11.4 M， PFS中位数为8.3 M（目前6 M PFS率为70.4%，12 M PFS率为42.7%），未达到OS。48.6%的患者经历G3或更高的治疗相关ae。具有良好的耐受性，pemb + plin和doc在临床获益后进展为ICI的转移性非小细胞肺癌患者中显示出良好的疗效。

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A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non-small cell lung cancer and progressive disease (PD) after immunotherapy (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy

Background

Immune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of NSCLC. Once progressed, it is not recommended to continue using ICI monotherapy, and the efficacy of chemotherapy is limited (ORR ∼10% with doc), so there is a high unmet clinical need. Plin is a selective immunomodulating microtubule-binding agent which promotes dendritic cell maturation and enhances anti-tumor T cell response, and have the potential to overcome immunotherapy resistance as a novel regimen in combination with pemb and doc. This phase 2 study was aimed to evaluate the efficacy and safety of pemb plus plin and doc in pts with metastatic NSCLC who had progressed after ICI.

Methods

In this investigator-initiated, single-arm, open-label, phase 2 trial, metastatic NSCLC pts who acquired resistance after ICI treatment were enrolled (Clinical trial information: NCT05599789). Participants received pemb 200 mg D1, plin 30 mg/m2 D1 and doc 75 mg/m2 D1 intravenously for a 21-day cycle. The primary endpoint was investigator-based ORR per RECIST 1.1. The secondary endpoints included PFS, OS, DoR and toxicity. Kaplan-Meier method is used for OS, PFS, and DOR analysis. The study intends to enroll 47 patients with a formal interim analysis at 19 patients enrolled.

Findings

38 pts were enrolled and 35 pts evaluable ITT population were analyzed at data cutoff on 10/10/2024. Median follow-up was 8.8 months (M) and median age was 68.0 (50-83) with 77.1% male and 22.9% female. 65.7% were current or former smokers. Histology included 60% with non-squamous, 40% with squamous cell carcinoma. Confirmed ORR was 18.2%. DCR was 89.7% (defined as PR and SD > 4 M), median DoR was 11.4 M, median PFS was 8.3 M (current 6 M PFS rate was 70.4%, 12 M PFS rate was 42.7%), and OS had not been reached. 48.6% of pts experienced G3 or higher treatment-related AEs.

Interpretation

With good tolerability, pemb plus plin and doc in pts with metastatic NSCLC who progressed after clinical benefit to ICI demonstrated promising efficacy.

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来源期刊

The Lancet Regional Health: Western Pacific Medicine-Pediatrics, Perinatology and Child Health

CiteScore

8.80

自引率

2.80%

发文量

305

审稿时长

11 weeks

期刊介绍： The Lancet Regional Health – Western Pacific, a gold open access journal, is an integral part of The Lancet's global initiative advocating for healthcare quality and access worldwide. It aims to advance clinical practice and health policy in the Western Pacific region, contributing to enhanced health outcomes. The journal publishes high-quality original research shedding light on clinical practice and health policy in the region. It also includes reviews, commentaries, and opinion pieces covering diverse regional health topics, such as infectious diseases, non-communicable diseases, child and adolescent health, maternal and reproductive health, aging health, mental health, the health workforce and systems, and health policy.