Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
Porustobart (HBM4003) plus Toripalimab as Second-Line Therapy in Patients with Advanced Hepatocellular Carcinoma: A Multicenter, Open-Label, Phase I Study.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Zhang Ningning, Liu Tian, Luo Ming, Hao Jihui, Qin Shukui, Zhang Yanqiao, Wang Gang, Chen Yajin, Zhang Jingdong, Gu Shanzhi, Niu Junqi, Xin Guijie, Yu Ge, Guo Yabing, Xu Chongyuan, Yao Jun, Shen Jie, Xu Aibing, Zhang Shuwen, Yang Di, Gao Meijuan, Luo Ruixuan, He Yebo, Zheng Fei, Cao Nan, Tao Xiaolu
Аннотация
PURPOSE: The study was conducted to evaluate porustobart (HBM4003), a novel anti-cytotoxic T lymphocyte-associated protein 4 monoclonal antibody, combined with toripalimab as second-line therapy in advanced hepatocellular carcinoma (HCC).
PATIENTS AND METHODS: This phase I study included two cohorts of patients with advanced HCC: cohort 1 included patients who were anti-PD-1/PD-L1 naïve and had received first-line anti-VEGFR tyrosine kinase inhibitor, and cohort 2 included patients who had failed prior first-line anti-PD-1/PD-L1 and anti-VEGF/VEGFR therapies. Porustobart (0.45 mg/kg) and toripalimab (240 mg) were administered every 21 days. The primary endpoint was the objective response rate (ORR).
RESULTS: In total, 16 patients were enrolled in cohort 1 and 12 in cohort 2. In the 26 patients with evaluable efficacy data, the ORR was 23.1% (95% confidence interval, 9.0-43.6). Cohort 1 exhibited an ORR of 40.0%, whereas cohort 2 presented no objective response. The median progression-free survival was 4.2 months, with 5.7 months for cohort 1 and 3.8 months for cohort 2. Biomarker exploration revealed higher abundance of intratumoral regulatory T cells in responders before treatment and a substantial elevation of CD4+Ki67+ and CD8+Ki67+ T cells after treatment. For safety, treatment-emergent adverse events were reported in 27 patients (96.4%), and treatment-related adverse events were reported in 25 patients (89.3%), among whom 13 (46.5%) had grade ≥3 treatment-related adverse events. Serious adverse events were observed in 12 patients (42.9%), and treatment-related serious adverse events were observed in nine patients (32.1%).
CONCLUSIONS: The combination of porustobart and toripalimab shows promising efficacy as a second-line therapy in anti-PD-1/PD-L1-naïve patients with advanced HCC and a manageable safety profile.
PATIENTS AND METHODS: This phase I study included two cohorts of patients with advanced HCC: cohort 1 included patients who were anti-PD-1/PD-L1 naïve and had received first-line anti-VEGFR tyrosine kinase inhibitor, and cohort 2 included patients who had failed prior first-line anti-PD-1/PD-L1 and anti-VEGF/VEGFR therapies. Porustobart (0.45 mg/kg) and toripalimab (240 mg) were administered every 21 days. The primary endpoint was the objective response rate (ORR).
RESULTS: In total, 16 patients were enrolled in cohort 1 and 12 in cohort 2. In the 26 patients with evaluable efficacy data, the ORR was 23.1% (95% confidence interval, 9.0-43.6). Cohort 1 exhibited an ORR of 40.0%, whereas cohort 2 presented no objective response. The median progression-free survival was 4.2 months, with 5.7 months for cohort 1 and 3.8 months for cohort 2. Biomarker exploration revealed higher abundance of intratumoral regulatory T cells in responders before treatment and a substantial elevation of CD4+Ki67+ and CD8+Ki67+ T cells after treatment. For safety, treatment-emergent adverse events were reported in 27 patients (96.4%), and treatment-related adverse events were reported in 25 patients (89.3%), among whom 13 (46.5%) had grade ≥3 treatment-related adverse events. Serious adverse events were observed in 12 patients (42.9%), and treatment-related serious adverse events were observed in nine patients (32.1%).
CONCLUSIONS: The combination of porustobart and toripalimab shows promising efficacy as a second-line therapy in anti-PD-1/PD-L1-naïve patients with advanced HCC and a manageable safety profile.