Neoadjuvant chemoradiotherapy plus sintilimab in pMMR/MSS rectal cancer patients with PD-L1 TPS ≥ 1% or CPS ≥ 1: an open-label, prospective, phase II study

Abstract 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 (T...

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Main Authors: Zhenlin Hou, Leen Liao, Weiwei Xiao, Qiaoqi Sui, Kai Han, Binyi Xiao, Yuan Li, Weijian Mei, Jiehai Yu, Zhigang Hong, Qichen Chen, Ruyue Song, Dandan Li, Xiaoshi Zhang, Qiaoxuan Wang, Zhizhong Pan, Wu Jiang, Peirong Ding
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-01018-0
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Summary:Abstract 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.
ISSN:2397-768X