Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, China.
Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China.
Cancer Immunol Immunother. 2024 Sep 5;73(11):219. doi: 10.1007/s00262-024-03806-2.
Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MER), VEGFR-2, KIT, and MET. SAFFRON-104 (NCT03941873) was a multicohort phase Ib/II study investigating sitravatinib with/without tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody, in patients with advanced hepatocellular carcinoma (HCC) or gastric cancer/gastroesophageal junction cancer (GC/GEJC).
Eligible patients had histologically/cytologically confirmed advanced HCC or GC/GEJC. Phase I determined the recommended phase II dose (RP2D) of sitravatinib with/without tislelizumab. Phase II evaluated sitravatinib monotherapy in patients with pretreated HCC, and sitravatinib plus tislelizumab in anti-PD-(L)1-naïve or -treated HCC and anti-PD-(L)1-naïve GC/GEJC. Primary endpoints were safety/tolerability (phase I) and objective response rate (ORR) (phase II).
At data cutoff (March 31, 2023), 111 patients were enrolled; 102 were efficacy-evaluable (median study follow-up 9.1 months [range: 0.7-36.9]). The RP2D of sitravatinib was determined as 120 mg orally once daily. In patients receiving sitravatinib monotherapy and sitravatinib in combination with tislelizumab, grade ≥ 3 treatment-related adverse events occurred in 14 (51.9%) and 42 (50.0%) patients, respectively. The ORR was 25% (95% confidence interval [CI]: 8.7-49.1) in patients with pretreated HCC receiving sitravatinib monotherapy. In patients receiving sitravatinib with tislelizumab, the ORR was 11.5% (95% CI 2.4-30.2) with anti-PD-(L)1-naïve HCC, 9.5% (95% CI 1.2-30.4) with anti-PD-(L)1-treated HCC, and 16.1% (95% CI 5.5-33.7) in patients with anti-PD-(L)1-naïve GC/GEJC.
Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.
西他拉替尼是一种针对 TAM（TYRO3、AXL、MER）、VEGFR-2、KIT 和 MET 的谱选择性酪氨酸激酶抑制剂。SAFFRON-104（NCT03941873）是一项多队列 Ib/II 期研究，评估了西他拉替尼联合/不联合抗程序性死亡蛋白 1（PD-1）抗体 tislelizumab 治疗晚期肝细胞癌（HCC）或胃癌/胃食管交界处癌（GC/GEJC）患者的疗效。
符合条件的患者均经组织学/细胞学证实患有晚期 HCC 或 GC/GEJC。I 期确定了西他拉替尼联合/不联合 tislelizumab 的推荐 II 期剂量（RP2D）。II 期评估了西他拉替尼治疗预处理 HCC 患者的疗效，以及西他拉替尼联合 tislelizumab 治疗抗 PD-(L)1 初治或经治 HCC 和抗 PD-(L)1 初治 GC/GEJC 患者的疗效。主要终点为安全性/耐受性（I 期）和客观缓解率（ORR）（II 期）。
截至数据截止日期（2023 年 3 月 31 日），共纳入 111 例患者；102 例患者可进行疗效评估（中位研究随访 9.1 个月[范围：0.7-36.9]）。西他拉替尼的 RP2D 确定为 120mg 口服，每日一次。接受西他拉替尼单药治疗和西他拉替尼联合 tislelizumab 治疗的患者中，分别有 14 例（51.9%）和 42 例（50.0%）患者发生≥3 级治疗相关不良事件。接受西他拉替尼单药治疗的预处理 HCC 患者的 ORR 为 25%（95%CI：8.7-49.1）。接受西他拉替尼联合 tislelizumab 治疗的患者中，抗 PD-(L)1 初治 HCC 的 ORR 为 11.5%（95%CI：2.4-30.2），抗 PD-(L)1 经治 HCC 的 ORR 为 9.5%（95%CI：1.2-30.4），抗 PD-(L)1 初治 GC/GEJC 的 ORR 为 16.1%（95%CI：5.5-33.7）。
西他拉替尼联合/不联合 tislelizumab 治疗晚期 HCC 和 GC/GEJC 患者耐受性良好，具有初步抗肿瘤活性。
