Efficacy and safety of tislelizumab as neoadjuvant therapy combined with MRD monitoring in locally advanced dMMR/MSI-H colon cancer: A prospective pilot study.

Abstract

3651 Background: PD-1 blockade has demonstrated high efficacy in metastatic and neoadjuvant settings for dMMR/MSI-H colorectal cancer. This study aimed to evaluate the efficacy and safety profile of neoadjuvant tislelizumab monotherapy in locally advanced dMMR/MSI-H colon cancer patients, with integrated minimal residual disease (MRD) monitoring. Methods: Histologically confirmed locally advanced dMMR/MSI-H colon adenocarcinoma are eligible for enrollment. Participants received 4 cycles of neoadjuvant tislelizumab (200 mg IV Q3W) followed by clinical response assessment. Patients continued receiving 4 additional cycles or underwent radical surgery based on the multidisciplinary team (MDT) decision. Non-operative management (NOM) was a choice of cCR patients after 8 cycles of treatment. MRD status was assessed by a tumor-informed, bespoke ctDNA assay (HuaJianwei) at baseline, during and post-treatment. The primary endpoint was pCR rate. Secondary endpoints included cCR rate, MPR rate, DFS, NOM rate, biomarker exploration, and safety. Results: Forty patients were enrolled between November 2022 and May 2025 (median follow-up: 13.58 months) and one requested to withdraw from the study. Twenty-eight (71.8%) underwent surgery, including 8 patients who received less than 6 cycles of neoadjuvant therapy, 18 patients who completed 8 cycles, and 2 patients who received more than 8 cycles based on MDT decision. Of resected patients, 22 (78.6%) achieved pCR and 26 (92.9%) achieved MPR. Nine patients opted for NOM due to cCR, with an overall CR rate of 79.5%. Grade 3 irAEs occurred in 4 patients (10.3%), including pneumonitis (n=2), renal insufficiency (n=1), and stroke (n=1). No treatment-related deaths occurred. Baseline MRD testing was completed in 29 patients, 28 (96.6%) of whom were positive. Rapid clearance of MRD was observed in 48.3% (14/29) of patients after 1 cycle and 75.9% (22/29) of patients after 2 cycles. Only one patient (1/10) remained MRD-positive post-treatment due to pneumonitis-related therapy discontinuation. Conclusions: Neoadjuvant tislelizumab monotherapy confers favorable efficacy and a manageable safety profile in locally advanced dMMR/MSI-H colon cancer with high pCR rates and feasible NOM for cCR patients. MRD monitoring provides valuable, real-time assessment of treatment response to guide surgical and surveillance decisions. Longer follow-up is needed to confirm response durability, particularly in NOM patients. Clinical trial information: NCT06262581 .