Background

Advanced primary liver cancer patients with malignant ascites have a poor prognosis and lack effective treatment plans. This phase Ib study aims to explore the safety and clinical efficacy of intraperitoneal anti-programmed cell death protein 1 (PD-1) antibody in these patients.

Patients and methods

Patients received sintilimab 100 mg intraperitoneally plus best supportive care on days 1, 8, and 15 in three cycles of 4 weeks. The course was repeated every 28 days until intolerable toxicity had developed or disease progression. The primary endpoint was safety, while the secondary endpoints were objective response rate (ORR), ascites control rate (ACR), and overall survival (OS).

Results

From February 2021 through November 2022, a total of 21 patients (14 hepatocellular carcinoma and 7 cholangiocarcinoma) were enrolled to receive intraperitoneal sintilimab. Twelve patients had adverse events (AEs). The most common grade 3 AEs were fatigue, rash, and abdominal pain. No grade ≥4 AEs occurred in any patients. ORR was only evaluated in 13 patients, including partial response in 4, stable disease in 7, and progressive disease in 2. A reduction in the median maximum diameter of the tumor after treatment was observed; however, there was no statistical significance among patients. The objective remission rate of ascites was 43.75%, and the median OS for all 21 patients was 17.6 weeks.

Conclusions

This exploratory study represents the first trial to demonstrate the safety and clinical efficacy of intraperitoneal anti-PD-1 antibody administration. No unexpected safety concerns were identified. A large, multicenter, prospective study is needed to confirm the promising clinical efficacy.

中文翻译：

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腹腔注射PD-1单克隆抗体治疗晚期原发性肝癌伴恶性腹水：单臂、单中心、Ib期试验

背景

晚期原发性肝癌伴恶性腹水患者预后较差，缺乏有效的治疗方案。这项 Ib 期研究旨在探讨腹腔注射抗程序性细胞死亡蛋白 1 (PD-1) 抗体在这些患者中的安全性和临床疗效。

患者和方法

患者在第 1、8 和 15 天腹腔注射 100 mg 信迪利单抗，并接受最佳支持治疗，共 3 个周期，每周期 4 周。每 28 天重复一次该过程，直到出现无法耐受的毒性或疾病进展。主要终点是安全性，次要终点是客观缓解率（ORR）、腹水控制率（ACR）和总生存期（OS）。

结果

从2021年2月至2022年11月，共有21名患者（14名肝细胞癌和7名胆管癌）入组接受腹腔注射信迪利单抗。12 名患者出现不良事件 (AE)。最常见的 3 级 AE 是疲劳、皮疹和腹痛。所有患者均未发生 ≥4 级 AE。仅对 13 名患者进行了 ORR 评估，其中 4 名患者部分缓解，7 名患者病情稳定，2 名患者病情进展。观察到治疗后肿瘤中位最大直径减小；然而，患者之间没有统计学意义。腹水客观缓解率为43.75%，所有21名患者的中位OS为17.6周。

结论

这项探索性研究是第一个证明腹膜内抗 PD-1 抗体给药的安全性和临床疗效的试验。没有发现意外的安全问题。需要一项大型、多中心、前瞻性研究来证实有希望的临床疗效。