SAFFRON-104: a phase Ib/II study of sitravatinib alone or with tislelizumab in advanced hepatocellular carcinoma and gastric cancer/gastroesophageal junction cancer

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2024年9月5日

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Jin Li,
Yuxian Bai,
Zhendong Chen,
Jieer Ying,
Yabing Guo,
Weijia Fang,
Feng Zhang,
Jianping Xiong,
Tao Zhang,
Zhiqiang Meng,
Jingdong Zhang,
Zhenggang Ren,
Chunyi Hao,
Yajin Chen,
Xiaoyan Lin,
Hongming Pan,
Fuxiang Zhou,
Xin Li,
Fan Yu,
Juan Zhang,
Zhang Zhang,
Shukui Qin

摘要

Background

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).

Methods

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).

Results

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.

Conclusions

Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.