Hou Zhenlin, Liao Leen, Xiao Weiwei, Sui Qiaoqi, Han Kai, Xiao Binyi, Li Yuan, Mei Weijian, Yu Jiehai, Hong Zhigang, Chen Qichen, Song Ruyue, Li Dandan, Zhang Xiaoshi, Wang Qiaoxuan, Pan Zhizhong, Jiang Wu, Ding Peirong
Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
NPJ Precis Oncol. 2025 Jul 12;9(1):237. doi: 10.1038/s41698-025-01018-0.
This phase II clinical trial aimed to evaluate the efficacy and safety of neoadjuvant long-course chemoradiotherapy combined with sintilimab in mismatch repair-proficient (pMMR)/microsatellite-stable (MSS) locally advanced rectal cancer (LARC) patients with a PD-L1 tumor proportion score (TPS) ≥1% or combined positive score (CPS) ≥1. The primary endpoint was pathological complete response (pCR), and safety was assessed. This trial was registered on ClinicalTrials.gov (identifying number: NCT04833387) with the registration date of April 4, 2021. Although the target pCR rate was not fully achieved, a notable improvement was observed, with 7/20 (35.0%) patients achieving pCR in the intention-to-treat analysis. A trend toward higher pCR rates was observed in patients with PD-L1 CPS ≥ 5 than in those with CPS < 5 (50.0% vs. 27.3%, P = 0.311). Treatment-related adverse events occurred in 12 patients (60.0%), with no grade 4 events. Biomarker analysis revealed that higher CD3 (P < 0.001) and CD8 (P = 0.018) expression, along with lower TIM-3 (P = 0.017) expression in the stroma, was associated with higher pCR rates.
这项II期临床试验旨在评估新辅助长程放化疗联合信迪利单抗在错配修复功能正常（pMMR）/微卫星稳定（MSS）、程序性死亡配体1（PD-L1）肿瘤比例评分（TPS）≥1%或联合阳性评分（CPS）≥1的局部晚期直肠癌（LARC）患者中的疗效和安全性。主要终点为病理完全缓解（pCR），并对安全性进行评估。该试验已在ClinicalTrials.gov上注册（识别号：NCT04833387），注册日期为2021年4月4日。尽管未完全达到目标pCR率，但观察到显著改善，在意向性分析中，20例患者中有7例（35.0%）达到pCR。与CPS<5的患者相比，PD-L1 CPS≥5的患者pCR率有升高趋势（50.0%对27.3%，P=0.311）。12例患者（60.0%）发生了与治疗相关的不良事件，无4级事件。生物标志物分析显示，基质中较高的CD3（P<0.001）和CD8（P=0.018）表达以及较低的T细胞免疫球蛋白和粘蛋白域包含分子3（TIM-3）（P=0.017）表达与较高的pCR率相关。
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