Evaluating Safety and Clinical Activity of Front-line Treatment with Cadonilimab plus Chemotherapy in Advanced/Metastatic Nonsmall Cell Lung Cancer Harboring STK11 Genetic Aberration: A Protocol of Phase II Study

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer Pub Date : 2024-07-14 DOI:10.1016/j.cllc.2024.07.006

Huixin Jiang, Ni Sun, Ru Li, Wenhui Guan, Yue Zhu, Zhanhong Xie, Xiaohong Xie, Ming Liu, Xinqing Lin, Chengzhi Zhou

{"title":"Evaluating Safety and Clinical Activity of Front-line Treatment with Cadonilimab plus Chemotherapy in Advanced/Metastatic Nonsmall Cell Lung Cancer Harboring STK11 Genetic Aberration: A Protocol of Phase II Study","authors":"Huixin Jiang, Ni Sun, Ru Li, Wenhui Guan, Yue Zhu, Zhanhong Xie, Xiaohong Xie, Ming Liu, Xinqing Lin, Chengzhi Zhou","doi":"10.1016/j.cllc.2024.07.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Cadonilimab is a first-in-class bispecific PD-1/CTLA-4 antibody. Serine/threonine kinase (STK11) mutation was shown to be related to low PD-L1 expression and objective response rate (ORR) in nonsmall cell lung cancer (NSCLC), resulting in poor progression-free survival (PFS) and overall survival (OS). Herein, we hypothesized that combining cadonilimab with chemotherapy could enhance antitumor immunity and extend survival in these patients. Consequently, we designed this study to explore the clinical activity and safety of cadonilimab combined with chemotherapy in patients with advanced/metastatic NSCLC harboring STK11 alteration.</div></div><div><h3>Trial design</h3><div>This single-center, open-label, single-arm phase II trial is conducted at the first affiliated hospital of Guangzhou Medical University. Treatment-naïve advanced/metastatic NSCLC patients harboring STK11 mutation will be enrolled in this study. Eligible patients will receive either cadonilimab (10mg/kg on Day 1) plus pemetrexed (500 mg/m<sup>2</sup>) and carboplatin (AUC = 5) for nonsquamous NSCLC or abraxane (100 mg/m<sup>2</sup>) and carboplatin (AUC = 5) for squamous NSCLC for 4 cycles, followed by maintenance therapy (cadonilimab plus pemetrexed or abraxane). The treatment will be discontinued when disease progression, intolerability to cadonilimab, and/or chemotherapy occurs. Measurable lesions were assessed according to the Response Evaluation Criteria in Solid Tumors (1.1). The main endpoint is ORR and safety. Subordinate endpoints include PFS, disease control rate, and duration of response.</div></div><div><h3>Results</h3><div>The study commenced enrolment in September 2023, with preliminary findings regarding the primary endpoint anticipated by January 2025.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages e393-e396"},"PeriodicalIF":3.3000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical lung cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1525730424001438","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Cadonilimab is a first-in-class bispecific PD-1/CTLA-4 antibody. Serine/threonine kinase (STK11) mutation was shown to be related to low PD-L1 expression and objective response rate (ORR) in nonsmall cell lung cancer (NSCLC), resulting in poor progression-free survival (PFS) and overall survival (OS). Herein, we hypothesized that combining cadonilimab with chemotherapy could enhance antitumor immunity and extend survival in these patients. Consequently, we designed this study to explore the clinical activity and safety of cadonilimab combined with chemotherapy in patients with advanced/metastatic NSCLC harboring STK11 alteration.

Trial design

This single-center, open-label, single-arm phase II trial is conducted at the first affiliated hospital of Guangzhou Medical University. Treatment-naïve advanced/metastatic NSCLC patients harboring STK11 mutation will be enrolled in this study. Eligible patients will receive either cadonilimab (10mg/kg on Day 1) plus pemetrexed (500 mg/m²) and carboplatin (AUC = 5) for nonsquamous NSCLC or abraxane (100 mg/m²) and carboplatin (AUC = 5) for squamous NSCLC for 4 cycles, followed by maintenance therapy (cadonilimab plus pemetrexed or abraxane). The treatment will be discontinued when disease progression, intolerability to cadonilimab, and/or chemotherapy occurs. Measurable lesions were assessed according to the Response Evaluation Criteria in Solid Tumors (1.1). The main endpoint is ORR and safety. Subordinate endpoints include PFS, disease control rate, and duration of response.

Results

The study commenced enrolment in September 2023, with preliminary findings regarding the primary endpoint anticipated by January 2025.

查看原文本刊更多论文

评估卡多尼单抗联合化疗一线治疗携带 STK11 基因畸变的晚期/转移性非小细胞肺癌的安全性和临床活性：II期研究方案

背景卡多尼单抗是第一类双特异性PD-1/CTLA-4抗体。在非小细胞肺癌（NSCLC）中，丝氨酸/苏氨酸激酶（STK11）突变与PD-L1低表达和客观反应率（ORR）有关，导致无进展生存期（PFS）和总生存期（OS）较差。在此，我们假设将卡多尼单抗与化疗联合使用可增强抗肿瘤免疫力，延长这些患者的生存期。因此，我们设计了这项研究来探讨卡多尼单抗联合化疗治疗携带STK11改变的晚期/转移性NSCLC患者的临床活性和安全性。本研究将招募携带STK11基因突变的治疗无效的晚期/转移性NSCLC患者。符合条件的患者将接受卡多尼单抗（第1天10毫克/千克）加培美曲塞（500毫克/平方米）和卡铂（AUC=5）治疗非鳞状NSCLC，或接受阿布拉克辛（100毫克/平方米）和卡铂（AUC=5）治疗鳞状NSCLC，共4个周期，然后接受维持治疗（卡多尼单抗加培美曲塞或阿布拉克辛）。当出现疾病进展、对卡多尼单抗不耐受和/或化疗时，将停止治疗。可测量病灶根据实体瘤反应评估标准（1.1）进行评估。主要终点是ORR和安全性。结果该研究于2023年9月开始入组，预计2025年1月得出主要终点的初步结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical lung cancer 医学-肿瘤学

CiteScore

7.00

自引率

2.80%

发文量

159

审稿时长

24 days

期刊介绍： Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.