Iparomlimab/Tuvonralimab Integrating With Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer (IT-TNT)
Trial Parameters
Brief Summary
In colorectal cancer (CRC), ICIs show strong therapeutic associations with microsatellite instability-high (MSI-H) status, while patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors exhibit poor responses. Dual immunotherapy may represent a promising strategy for MSS populations. The Dutch NICHE trial reported a 27% pathological response rate (4/15) in MSS CRC patients with clinical stage I-III disease treated with neoadjuvant ipilimumab plus nivolumab. In advanced or metastatic CRC, a study by Jin Li et al. demonstrated that iparomlimab/tuvonralimab combined with bevacizumab and the XELOX regimen achieved an objective response rate of 70.6% (95% CI: 56.2%-82.5%). Radiotherapy may synergize with ICIs through multiple immunomodulatory mechanisms. For pMMR/MSS LARC, combining CRT with ICIs holds promise to overcome the "immune-cold" tumor microenvironment and improve therapeutic efficacy. In this clinical trial, the investigators aim to evaluate the efficacy and safety of integrating immunotherapy with CRT as a novel total neoadjuvant therapy for pMMR/MSS rectal cancer.
Eligibility Criteria
Inclusion Criteria: 1. Age 18-75 years old, male and female 2. Histologically confirmed pMMR/MSS rectal adenocarcinoma, defined by MRI as clinical stage II (T3-4, N-) or stage III (any T, N+) 3. Tumor within 12 cm of the anal verge with at least one of the following high-risk factors: cT4, cN2, extramural vascular invasion \[EMVI+\], mesorectal fascia involved \[MRF+\], lateral lymph node \[LN+\], tumor deposit, or low rectal cancer (≤5 cm from the anal verge) 4. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. 5. No evidence of distant metastases based on chest and abdominal CT or whole body PET-CT examinations 6. No other rectal cancer (e.g., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, neuroendocrine carcinoma, etc.) or synchronous colon cancer 7. Presence of measurable lesions that meet RECIST v1.1 criteria for evaluation. Exclusion Criteria: 1. dMMR or MSI-H patients 2. Myelosuppression without obvious causes 3. Locally advanced rectal can