Neoadjuvant chemoradiotherapy combined with tislelizumab for locally advanced rectal cancer: A phase II clinical trial.

e15624 Background: Surgical resection remains the cornerstone treatment for locally advanced rectal cancer. However, for patients at high risk of recurrence, even with resectable tumors, the prognosis is still unfavorable. PD-1 inhibitors have shown promise in treating dMMR/MSI-H advanced metastatic rectal cancer, achieving an objective response rate of 30%-40% in patients who have previously failed treatments. This clinical trial aims to evaluate the efficacy and safety of combining tislelizumab (an anti-PD-1 antibody) with concurrent chemoradiotherapy as neoadjuvant therapy for patients with locally advanced rectal cancer. Methods: In this phase II clinical trial (ChiCTR2400094540), patients with resectable rectal cancer were divided into two parallel cohorts (1:1) based on different neoadjuvant treatment protocols. Patients in group A received chemoradiotherapy combined with tislelizumab, while patients in Group B received chemoradiotherapy alone. All patients were scheduled to undergo radical surgery after completing neoadjuvant treatment. The primary endpoint was the pathological complete response (pCR) rate. In addition, whole-exome, transcriptome, and immune repertoire sequencing technologies were utilized to explore potential biomarkers and changes in the immune microenvironment associated with the prognosis of neoadjuvant treatment in rectal cancer patients. Results: As of November 30, 2024, a total of 28 patients were enrolled in this study, with 16 in the experimental group and 12 in the control group. Of these, 26 patients completed surgical treatment, while 2 patients in the control group did not undergo surgery. There were notable differences in tumor regression grade (TRG) and lymph node remnants between the two groups. Due to the small sample size, no significant difference was observed in pCR rates between the groups (31.2% vs 30%). However, a difference was noted in major pathological response (MPR) rates (68.8% vs 30%). Tumor-associated macrophage M2 may influence prognosis. Both a low positive rate of tumor parenchyma and a high positive rate of tumor interstitial tissue were indicative of a better prognosis, although no significant difference was found. Conclusions: For patients with locally advanced rectal cancer, the addition of tislelizumab to neoadjuvant chemoradiotherapy appears to increase the rates of pathological complete response (pCR) and major pathological response (MPR), although further research is needed to confirm these findings. Clinical trial information: ChiCTR2400094540 .