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特瑞普利单抗注射液（拓益^®）作为我国批准上市的首个国产以PD-1为靶点的单抗药物，获得国家科技重大专项项目支持，并荣膺国家专利领域最高奖项“中国专利金奖”。

特瑞普利单抗至今已在全球（包括中国、美国、东南亚及欧洲等地）开展了覆盖超过15个适应症的40多项由公司发起的临床研究。正在进行或已完成的关键注册临床研究在多个瘤种范围内评估特瑞普利单抗的安全性及疗效，包括肺癌、鼻咽癌、食管癌、胃癌、膀胱癌、乳腺癌、肝癌、肾癌及皮肤癌等。

截至目前，特瑞普利单抗已在中国内地获批12项适应症：【1】用于既往接受全身系统治疗失败的不可切除或转移性黑色素瘤的治疗（2018年12月）；【2】用于既往接受过二线及以上系统治疗失败的复发/转移性鼻咽癌患者的治疗（2021年2月）；【3】用于含铂化疗失败包括新辅助或辅助化疗12个月内进展的局部晚期或转移性尿路上皮癌的治疗（2021年4月）；【4】联合顺铂和吉西他滨用于局部复发或转移性鼻咽癌患者的一线治疗（2021年11月）；【5】联合紫杉醇和顺铂用于不可切除局部晚期/复发或远处转移性食管鳞癌患者的一线治疗（2022年5月）；【6】联合培美曲塞和铂类用于表皮生长因子受体（EGFR）基因突变阴性和间变性淋巴瘤激酶（ALK）阴性、不可手术切除的局部晚期或转移性非鳞状非小细胞肺癌的一线治疗（2022年9月）；【7】联合化疗围手术期治疗，继之本品单药作为辅助治疗，用于可切除IIIA-IIIB期非小细胞肺癌的成人患者（2023年12月）；【8】联合阿昔替尼用于中高危的不可切除或转移性肾细胞癌患者的一线治疗（2024年4月）；【9】联合依托泊苷和铂类用于广泛期小细胞肺癌一线治疗（2024年6月）；【10】联合注射用紫杉醇（白蛋白结合型）用于经充分验证的检测评估PD-L1阳性（CPS≥1）的复发或转移性三阴性乳腺癌的一线治疗（2024年6月）；【11】联合贝伐珠单抗用于不可切除或转移性肝细胞癌患者的一线治疗（2025年3月）；【12】用于不可切除或转移性黑色素瘤的一线治疗(2025年4月)。2020年12月，特瑞普利单抗首次通过国家医保谈判，目前已有10项获批适应症纳入《国家医保目录（2024年）》，是目录中唯一用于黑色素瘤、非小细胞肺癌围手术期、肾癌、三阴性乳腺癌治疗的抗PD-1单抗药物。2024年10月，特瑞普利单抗用于复发/转移性鼻咽癌治疗的适应症在中国香港获批。

在国际化布局方面，特瑞普利单抗目前已在美国、欧盟、印度、英国、约旦、澳大利亚、新加坡等国家和地区获得批准上市，并在全球多个国家和地区接受上市审评。

作用机制

PD-1为T细胞表面受体，是T细胞共抑制信号通路的一种免疫检查点分子。如图下部分所示，当PD-1与肿瘤细胞表面的配体PD-L1/PD-L2结合，T细胞便接收抑制性信号。通过PD-1与其配体结合致使T细胞免疫失能并因此阻断抗肿瘤反应。抗PD-1单克隆抗体可阻断PD-1与PD-L1/PD-L2结合，从而使T细胞的免疫功能恢复。

主要研究文献

• 序号 期刊名称 文献标题 发表时间 链接
• 1 The Lancet Gastroenterology & Hepatology Toripalimab plus bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HEPATORCH): a randomised, open-label, phase 3 trial 2025 打开链接
• 2 JAMA Oncology Toripalimab For Extensive-Stage Small Cell Lung Cancer 2024 打开链接
• 3 Nature Medicine Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial 2024 打开链接
• 4 Journal of the American Medical Association Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial 2024 打开链接
• 5 Journal of the American Medical Association Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial 2023 打开链接
• 6 Annals of Oncology Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study 2023 打开链接
• 7 Cancer Cell Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial 2022 打开链接
• 8 Journal of Clinical Oncology Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01) 2022 打开链接
• 9 Journal for ImmunoTherapy of Cancer Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis 2022 打开链接
• 10 Clinical Cancer Research Safety, Efficacy, and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03 2022 打开链接
• 11 Annals of Oncology Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial 2022 打开链接
• 12 Nature Medicine Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial 2021 打开链接
• 13 Signal Transduction and Targeted Therapy Toripalimab plus chemotherapy as second-line treatment in previously EGFRTKIs treated patients with EGFR-mutant advanced NSCLC: a multi-center phase II trial 2021 打开链接
• 14 Journal of Clinical Oncology Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02) 2021 打开链接
• 15 JAMA Network Open Safety, Antitumor Activity, and Pharmacokinetics of Toripalimab, a Programmed Cell Death 1 Inhibitor, in Patients With Advanced Non–Small Cell Lung Cancer A Phase 1 Trial 2020 打开链接
• 16 Cancer Communications A Phase I Study of Toripalimab, an anti-PD-1 Antibody, in Patients With Refractory Malignant Solid Tumors 2020 打开链接
• 17 Clinical Cancer Research Safety, Efficacy and Biomarker Analysis of Toripalimab in previously treated advanced melanoma: results of the POLARIS-01 multicenter phase II trial 2020 打开链接
• 18 European Journal of Cancer Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study 2020 打开链接
• 19 mABs Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy 2019 打开链接
• 20 Acta Pharmacologica Sinica Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001 2017 打开链接
• 21 Clinical Cancer Research Efficacy, safety and biomarkers of toripalimab in patients with recurrent or metastatic neuroendocrine neoplasms：a multiple-center phase Ib trial 2020 打开链接
• 22 Journal of Clinical Oncology Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial 2019 打开链接
• 23 Annals of Translational Medicine JS001, an anti-PD-1 mAb for advanced triple negative breast cancer patients after multi-line systemic therapy in a phase I trial 2019 打开链接
• 24 Annals of Oncology Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemorefractory gastric cancer treated with toripalimab, a PD1 antibody in phase Ib/II clinical trial NCT02915432 2019 打开链接
• 25 Journal of Hematology & Oncology Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients 2019 打开链接