Cheng Ying, Wang Jie, Yu Yan, Wang QiMing, Yang Runxiang, Xia Bing, Li Chong, Lv Dongqing, Yi Tienan, Han Liang, Liu Xiao-Qing, Wang Xi-Cheng, Zhang Wei, Su Man, Shen Minjie, Xu Jing, Peng Bang An
Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China.
Department of Medical Oncology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Clin Cancer Res. 2025 Jul 15;31(14):2926-2934. doi: 10.1158/1078-0432.CCR-25-0022.
Tifcemalimab is a recombinant humanized IgG4k monoclonal antibody targeting B- and T-lymphocyte attenuator. Co-blockade of B- and T-lymphocyte attenuator and programmed death-1 pathways improved outcomes in nonclinical models. This phase I/II trial evaluated the safety and preliminary efficacy of tifcemalimab plus toripalimab in advanced lung cancer.
Eligible patients with pathologically confirmed advanced non-small cell lung cancer (NSCLC) without sensitive EGFR variation and anaplastic lymphoma kinase fusion who failed standard treatment including one PD-1/PD-L1 inhibitor or those with refractory extensive-stage small cell lung cancer (SCLC) received tifcemalimab (200 mg) and toripalimab (240 mg) every 3 weeks intravenously until disease progression or intolerable toxicity. The Simon two-stage optimal design was used in the expansion part. The primary endpoints included safety and objective response rate (ORR) per RECIST version 1.1.
Twenty-four patients with NSCLC and 43 with SCLC were enrolled (median age of all patients, 60.0 years). All patients with NSCLC and 14 (32.6%) with SCLC had received previous immunotherapy. Fifty-five (82.1%) patients experienced treatment-related adverse events, and five (7.5%) patients reported grade ≥3 immune-related adverse events. For NSCLC, the ORR was 4.3%, and disease control rate was 47.8%. The median progression-free survival and overall survival were 1.5 and 18.9 months, respectively. For SCLC, the ORR and disease control rate were 35.0% and 55.0%, respectively. The median duration of response, progression-free survival, and overall survival were 5.7, 2.8, and 12.3 months, respectively.
Tifcemalimab plus toripalimab showed promising antitumor activities with acceptable safety, especially in advanced refractory SCLC.
替夫西单抗是一种靶向B和T淋巴细胞衰减器的重组人源化IgG4k单克隆抗体。在非临床模型中，联合阻断B和T淋巴细胞衰减器与程序性死亡-1通路可改善治疗结果。这项I/II期试验评估了替夫西单抗联合托瑞帕利单抗治疗晚期肺癌的安全性和初步疗效。
符合条件的患者为经病理确诊的晚期非小细胞肺癌（NSCLC），无敏感表皮生长因子受体（EGFR）变异和间变性淋巴瘤激酶融合，且接受过包括一种程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）抑制剂在内的标准治疗后失败，或为难治性广泛期小细胞肺癌（SCLC）患者，每3周静脉注射替夫西单抗（200 mg）和托瑞帕利单抗（240 mg），直至疾病进展或出现无法耐受的毒性。扩展部分采用西蒙两阶段最优设计。主要终点包括安全性和根据实体瘤疗效评价标准（RECIST）1.1版的客观缓解率（ORR）。
纳入24例NSCLC患者和43例SCLC患者（所有患者的中位年龄为60.0岁）。所有NSCLC患者和14例（32.6%）SCLC患者既往均接受过免疫治疗。55例（82.1%）患者发生治疗相关不良事件，5例（7.5%）患者报告了≥3级免疫相关不良事件。对于NSCLC，ORR为4.3%，疾病控制率为47.8%。中位无进展生存期和总生存期分别为个月和18.9个月。对于SCLC，ORR和疾病控制率分别为35.0%和55.0%。中位缓解持续时间、无进展生存期和总生存期分别为5.7个月、2.8个月和12.3个月。
替夫西单抗联合托瑞帕利单抗显示出有前景的抗肿瘤活性，安全性可接受，尤其是在晚期难治性SCLC中。
