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

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.

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Publication Details

Journal
Cancer Immunology Immunotherapy
Published
2024-09-05
DOI
https://doi.org/10.1007/s00262-024-03806-2
Citations
12
Primary Topic
Gastric Cancer Management and Outcomes
Type
article
Field-Weighted Citation Impact
5.03

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article

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

Weijia Fang, Zhenggang Ren, Shukui Qin, Hongming Pan et al.
12 citations
Cancer Immunology Immunotherapy
Gastric Cancer Management and Outcomes
5.03
article

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

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

Abstract

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.

Cancer Immunology ImmunotherapyVol. 73(11)
Fujian Medical University (CN), Union Hospital (HK), Nanchang University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Anhui Medical University (CN), Peking University (CN), Fudan University (CN), Sir Run Run Shaw Hospital (CN), Wuhan University (CN), Fudan University Shanghai Cancer Center (CN), Peking University Cancer Hospital (CN), Sun Yat-sen Memorial Hospital (CN), Zhejiang Cancer Hospital (CN), BeiGene (China) (CN), Nanfang Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Zhongnan Hospital of Wuhan University (CN), Zhongshan Hospital (CN), Shanghai East Hospital (CN), Jiangsu Cancer Hospital (CN), Second Affiliated Hospital of Anhui Medical University (CN), Hubei Cancer Hospital (CN), Liaoning Cancer Hospital & Institute (CN), Union Hospital (CN), First Affiliated Hospital of Nanchang University (CN), Huazhong University of Science and Technology (CN), Southern Medical University (CN), Zhejiang University (CN), China Medical University (CN)
BeiGene
Good health and well-being
Openalex Percentile: Top 4%
Gastric Cancer Management and Outcomes
5.03
DOIOpen Access PDFOpenAlex
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