Eftilagimod Alpha（一种可溶性 LAG-3 蛋白）与 Pembrolizumab 联合用于抗程序性细胞死亡蛋白 1/程序性死亡配体 1 治疗难治的二线转移性 NSCLC：2 期研究的最终结果

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2024-08-30 DOI:10.1016/j.jtocrr.2024.100725

Matthew G. Krebs MD , Martin Forster MD, PhD , Margarita Majem MD, PhD , Julio Peguero MD , Wade Iams MD , Tim Clay MD , Patricia Roxburgh MD, PhD , Bernard Doger MD, PhD , Pawan Bajaj MD , Andres Barba MD , Suvini Perera MS , Christian Mueller MS , Frédéric Triebel MD, PhD

{"title":"Eftilagimod Alpha（一种可溶性 LAG-3 蛋白）与 Pembrolizumab 联合用于抗程序性细胞死亡蛋白 1/程序性死亡配体 1 治疗难治的二线转移性 NSCLC：2 期研究的最终结果","authors":"Matthew G. Krebs MD , Martin Forster MD, PhD , Margarita Majem MD, PhD , Julio Peguero MD , Wade Iams MD , Tim Clay MD , Patricia Roxburgh MD, PhD , Bernard Doger MD, PhD , Pawan Bajaj MD , Andres Barba MD , Suvini Perera MS , Christian Mueller MS , Frédéric Triebel MD, PhD","doi":"10.1016/j.jtocrr.2024.100725","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4<sup>+</sup> and CD8<sup>+</sup>) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti–PD-(L)1-refractory metastatic patients with NSCLC.</div></div><div><h3>Methods</h3><div>After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally.</div></div><div><h3>Results</h3><div>Thirty-six patients were enrolled from April 2019 to August 2021 using Simon’s two-stage design. Most patients (81.8%) had low or negative (<50%) PD-(L)1 tumor proportion score. First-line therapy was anti–PD-(L)1-based for all patients, combined with chemotherapy for 66.7%. The confirmed objective response and disease control rates were 8.3% and 33.3%. The median progression-free survival was 2.1 months and the median OS was 9.9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment.</div></div><div><h3>Conclusions</h3><div>Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100725"},"PeriodicalIF":3.0000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti–Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy: Final Results from a Phase 2 Study\",\"authors\":\"Matthew G. Krebs MD , Martin Forster MD, PhD , Margarita Majem MD, PhD , Julio Peguero MD , Wade Iams MD , Tim Clay MD , Patricia Roxburgh MD, PhD , Bernard Doger MD, PhD , Pawan Bajaj MD , Andres Barba MD , Suvini Perera MS , Christian Mueller MS , Frédéric Triebel MD, PhD\",\"doi\":\"10.1016/j.jtocrr.2024.100725\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4<sup>+</sup> and CD8<sup>+</sup>) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti–PD-(L)1-refractory metastatic patients with NSCLC.</div></div><div><h3>Methods</h3><div>After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally.</div></div><div><h3>Results</h3><div>Thirty-six patients were enrolled from April 2019 to August 2021 using Simon’s two-stage design. Most patients (81.8%) had low or negative (<50%) PD-(L)1 tumor proportion score. First-line therapy was anti–PD-(L)1-based for all patients, combined with chemotherapy for 66.7%. The confirmed objective response and disease control rates were 8.3% and 33.3%. The median progression-free survival was 2.1 months and the median OS was 9.9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment.</div></div><div><h3>Conclusions</h3><div>Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.</div></div>\",\"PeriodicalId\":17675,\"journal\":{\"name\":\"JTO Clinical and Research Reports\",\"volume\":\"5 11\",\"pages\":\"Article 100725\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JTO Clinical and Research Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S266636432400095X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266636432400095X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

导读：Eftilagimod alpha（efti）是一种可溶性淋巴细胞活化基因-3蛋白，可触发抗原递呈细胞和T细胞（CD4+和CD8+）活化，有助于克服程序性细胞死亡蛋白1或程序性细胞死亡配体1（PD-(L)1）抑制剂的耐药性。方法在抗PD-(L)1一线治疗确诊进展后，患者接受依夫替（30 毫克，每2 周皮下注射一次，8 个3 周周期，然后每3 周注射一次，最多54 周）和pembrolizumab（200 毫克，每3 周静脉注射一次，最多105 周）治疗。主要终点是根据修订后的实体瘤免疫疗法反应评估标准1.1版得出的客观反应率。次要终点包括疾病控制率、无进展生存期、总生存期（OS）和耐受性。探索性终点包括肿瘤生长动力学和预定义亚组分析。对程序性细胞死亡配体1肿瘤比例评分进行集中评估。结果从2019年4月到2021年8月，采用西蒙两阶段设计入组了36名患者。大多数患者（81.8%）的PD-（L）1肿瘤比例评分较低或为阴性（<50%）。所有患者的一线治疗均以抗PD-（L）1为基础，66.7%的患者联合化疗。确诊客观反应率和疾病控制率分别为8.3%和33.3%。中位无进展生存期为2.1个月，中位OS为9.9个月。PD-(L)1高表达或对PD-(L)1抑制剂获得性耐药的患者显示出更优越的反应和生存结果，而OS与疾病控制密切相关。结论Efti加pembrolizumab对PD-（L）1抑制剂耐药的NSCLC患者耐受性良好，并显示出抗肿瘤活性迹象，值得进一步研究。试验注册号：NCT03625323：NCT03625323。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti–Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy: Final Results from a Phase 2 Study

Introduction

Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4⁺ and CD8⁺) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti–PD-(L)1-refractory metastatic patients with NSCLC.

Methods

After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally.

Results

Thirty-six patients were enrolled from April 2019 to August 2021 using Simon’s two-stage design. Most patients (81.8%) had low or negative (<50%) PD-(L)1 tumor proportion score. First-line therapy was anti–PD-(L)1-based for all patients, combined with chemotherapy for 66.7%. The confirmed objective response and disease control rates were 8.3% and 33.3%. The median progression-free survival was 2.1 months and the median OS was 9.9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment.

Conclusions

Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊