对于晚期食管鳞状细胞癌 (ESCC) 和肝细胞癌 (HCC) 来说，有效的全身治疗仍然有限，特别是在之前使用免疫检查点抑制剂 (ICIs) 治疗失败后。理论上，酪氨酸激酶抑制剂 (TKI) 与 ICI 的组合可能会恢复免疫治疗的敏感性。 在这项 1b 期研究中，患者接受了 AL2846，这是一种具有多个靶点（c-MET、VEGFR1、c-KIT、Axl、RET、KDR）的抗血管生成 TKI。和 VEGFR3），与抗 PD-L1 抗体（TQB2450）联合使用，直至疾病进展、无法耐受的毒性、死亡或因任何原因停药。主要终点包括总体缓解率 (ORR) 和安全性，次要终点包括无进展生存期 (PFS)、总体生存期 (OS)、疾病控制率 (DCR) 和缓解持续时间。2021 年 11 月至 9 月2022 年，入组了 18 名 ESCC 患者和 15 名 HCC 患者，其 ORR 分别为 11.1%（95% 置信区间 [CI]，3.1%-32.8%）和 0%。分别有 32 名患者 (97.0%) 和 31 名患者 (93.9%) 记录了任何级别的不良事件 (AE) 和治疗相关的 AE。 10 名患者（30.3%）观察到 3 级或以上 AE，其中呕吐（6.1%）和感染性肺炎（9.1%）最为常见。 ESCC 患者的中位 PFS 和 OS 值分别为 3.22 个月（95% CI，1.35-5.68 个月）和 5.98 个月（95% CI，3.71-8.87 个月），5.55 个月（95% CI，2.66 个月）。 HCC 患者的时间分别为不可评估 [NE]）和 16.72 个月（95% CI，4.86 个月至 NE）。 ESCC 患者的 DCR 为 66.7%（95% CI，43.75%-83.72%），HCC 患者的 DCR 为 73.3%（95% CI，48.05%-89.10%）。 TQB2450 和 AL2846 联合治疗在患有晚期 ESCC 和 HCC 的免疫治疗难治性患者。© 2024 作者。 《癌症》由 Wiley periodicals LLC 代表美国癌症协会出版。

Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity.In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response.Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC.Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.