Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Oncology, Henan Cancer Hospital, Zhengzhou 450003, China.
Cell Rep Med. 2023 Dec 19;4(12):101301. doi: 10.1016/j.xcrm.2023.101301. Epub 2023 Nov 27.
We report a multicenter, phase 2 study evaluating the efficacy of pucotenlimab, an anti-PD-1 antibody, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, and potential biomarkers for response. Overall, 100 patients with previously treated, advanced solid tumors centrally confirmed as dMMR or MSI-H received pucotenlimab at 200 mg every 3 weeks. The most common cancer type is colorectal cancer (n = 71). With a median follow-up of 22.5 months, the objective response rate is 49.0% (95% confidence interval 38.86%-59.20%) as assessed by the independent review committee, while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 patients. For the biomarker analysis, responders are enriched in patients with mutations in the KMT2D gene. Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.
我们报告了一项多中心、2 期研究，评估了抗 PD-1 抗体 pucotenlimab 在错配修复缺陷（dMMR）或微卫星不稳定高（MSI-H）肿瘤患者中的疗效，以及潜在的反应生物标志物。共有 100 名经中心确认患有先前治疗的晚期实体瘤且为 dMMR 或 MSI-H 的患者接受了每 3 周 200mg 的 pucotenlimab 治疗。最常见的癌症类型是结直肠癌（n=71）。在中位随访 22.5 个月时，独立审查委员会评估的客观缓解率为 49.0%（95%置信区间 38.86%-59.20%），而中位无进展生存期和总生存期尚未达到。18 名患者出现了≥3 级治疗相关不良事件。在生物标志物分析中，应答者在 KMT2D 基因突变的患者中更为丰富。pucotenlimab 是先前治疗的晚期 dMMR/MSI-H 实体瘤的有效治疗选择，KMT2D 突变的预测价值值得进一步研究。该研究在 ClinicalTrials.gov 上注册：NCT03704246。
