JAMA oncology · 2025
Sintilimab Plus Axitinib for Advanced Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Phase 2 Nonrandomized Clinical Trial.
Клиническое исследование II фазыСтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Zhang Xingming, Liu Haoyang, Liang Jiayu, Zhao Junjie, Wang Yongquan, Chen Yuntian, Kang Deying, Chen Qian, Zhang Yaowen, Yin Xiaoxue, Zeng Yuhao, Wang Zilin, Sheng Xinan, Yao Xin, Gong Kan, Liu Xiaodong, Chen Zhibin, Qiu Mingxing, Chen Wei, Wang Zongping, Luo Guangheng, Zhou Tingting, Yang Nanshan, Pan Xiuyi, Nie Ling, Zhang Mengni, Chen Junru, Zhao Jinge, Hu Xu, Xu Lijing, Tang Bo, Dai Jindong, Liu Haolin, Ni Yuchao, Huang Rui, Wei Qiang, Li Xiang, He Qiying, Liu Jiyan, Shen Pengfei, Chen Ni, Liu Zhenhua, Sun Guangxi, Yao Jin, Zeng Hao
Аннотация
IMPORTANCE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a lethal kidney cancer that has limited therapeutic options.
OBJECTIVE: To evaluate the efficacy and safety of sintilimab plus axitinib for treatment of advanced FH-deficient RCC.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2 multicenter, open-label, single-arm nonrandomized clinical trial enrolled patients with pathologically confirmed, treatment-naive, advanced FH-deficient RCC and an Eastern Cooperative Oncology Group Performance Status of 0 to 2 from July 1, 2021, to August 29, 2023, across 8 institutions in China. The data cutoff date was December 1, 2024.
INTERVENTION: Patients received sintilimab, 200 mg, intravenously every 3 weeks, combined with axitinib, 5 mg, orally twice daily, until disease progression, intolerable toxic effects, or withdrawal of consent.
MAIN OUTCOMES AND MEASURES: The primary end points were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1, and progression-free survival (PFS). Secondary end points included safety, overall survival, disease control rate (proportion of patients with complete or partial response or stable disease for ≥6 months), duration of response, and exploratory genomic-associated outcomes.
RESULTS: Of 52 patients screened for eligibility, 41 patients (median [range] age, 36 [18-75] years; 10 [24%] female) were enrolled. The median (range) duration of follow-up was 26.0 (0.7-41.6) months. Overall, ORR was 56% (23 patients; 95% CI, 40%-72%), with a median duration of response of not reached (NR; 95% CI, 23.3 months to NR). The disease control rate was 73% (30 patients). The median PFS was 19.8 months (95% CI, 10.9 months to NR). Patients with low somatic copy number alteration burden showed more favorable therapeutic outcomes. Thirteen patients (32%) experienced grade 3 or higher treatment-related adverse events, with the most frequent being hypertriglyceridemia in 3 (7%), rash in 2 (5%), and anemia in 2 (5%).
CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, the combination of sintilimab and axitinib demonstrated encouraging ORR and PFS with manageable safety profile in patients with FH-deficient RCC. This combination therapy warrants further validation in a randomized clinical trial.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04387500.
OBJECTIVE: To evaluate the efficacy and safety of sintilimab plus axitinib for treatment of advanced FH-deficient RCC.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2 multicenter, open-label, single-arm nonrandomized clinical trial enrolled patients with pathologically confirmed, treatment-naive, advanced FH-deficient RCC and an Eastern Cooperative Oncology Group Performance Status of 0 to 2 from July 1, 2021, to August 29, 2023, across 8 institutions in China. The data cutoff date was December 1, 2024.
INTERVENTION: Patients received sintilimab, 200 mg, intravenously every 3 weeks, combined with axitinib, 5 mg, orally twice daily, until disease progression, intolerable toxic effects, or withdrawal of consent.
MAIN OUTCOMES AND MEASURES: The primary end points were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1, and progression-free survival (PFS). Secondary end points included safety, overall survival, disease control rate (proportion of patients with complete or partial response or stable disease for ≥6 months), duration of response, and exploratory genomic-associated outcomes.
RESULTS: Of 52 patients screened for eligibility, 41 patients (median [range] age, 36 [18-75] years; 10 [24%] female) were enrolled. The median (range) duration of follow-up was 26.0 (0.7-41.6) months. Overall, ORR was 56% (23 patients; 95% CI, 40%-72%), with a median duration of response of not reached (NR; 95% CI, 23.3 months to NR). The disease control rate was 73% (30 patients). The median PFS was 19.8 months (95% CI, 10.9 months to NR). Patients with low somatic copy number alteration burden showed more favorable therapeutic outcomes. Thirteen patients (32%) experienced grade 3 or higher treatment-related adverse events, with the most frequent being hypertriglyceridemia in 3 (7%), rash in 2 (5%), and anemia in 2 (5%).
CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, the combination of sintilimab and axitinib demonstrated encouraging ORR and PFS with manageable safety profile in patients with FH-deficient RCC. This combination therapy warrants further validation in a randomized clinical trial.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04387500.