首次在人体动脉内给药 tislelizumab 治疗 pMMR 局部晚期直肠癌：单臂、开放标签 II 期临床试验

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-10-13 DOI:10.1016/j.tranon.2024.102154

Weina Yang , Chengyuan Qian , Jiamin Luo , Chuan Chen , Yan Feng , Nan Dai , Xuemei Li , He Xiao , Yuxin Yang , Mengxia Li , Chunxue Li , Dong Wang

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引用次数: 0

摘要

背景静脉注射免疫检查点抑制剂（ICIs）已显示出治疗局部晚期直肠癌（LARC）的疗效，但对全身毒性的担忧依然存在。本研究开发了一种独特的方法，称为经导管直肠动脉介入化疗免疫栓塞（CIETAI），旨在增强抗肿瘤反应，同时最大限度地减少全身毒性。既往未经治疗的II/III期LARC患者接受术前CIETAI联合PD-1抑制剂替斯利珠单抗加奥沙利铂治疗，随后接受标准同步化放疗（卡培他滨和50.4 Gy放射治疗）。结果2023年1月至2023年12月期间，共有38名患者入组。作为主要终点，17 名患者（44.74%）获得了病理完全反应（TRG0），主要病理反应（MPR）率为 65.79%。肛门保留率为 84.21%（32/38），重要的是，21 位低位直肠癌患者中有 15 位实现了器官保留和功能维持。8名患者出现了3-4级不良事件（AE）。所有与免疫相关的不良反应均为1-2级，最常见的是内分泌毒性（5/6，83.33%）。结论这项研究提供了初步证据，支持动脉内注射替斯利珠单抗在LARC新辅助治疗中的安全性和有效性。这些令人鼓舞的结果鼓励我们在更大的队列中进一步探索，以验证这种新型 CIETAI 策略的临床效果：NCT05957016。

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First in human intraarterial delivery of tislelizumab for the treatment of pMMR locally advanced rectal cancer: A single-arm, open label, phase II clinical trial

Background

Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity.

Method

This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles.

Results

Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3–4 adverse events (AEs). All immune-related AEs were grade 1–2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred.

Conclusion

This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy.

Trial registration

ClinicalTrials.gov Identifier: NCT05957016.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.