Iparomlimab/Tuvonralimab Integrating With Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer (IT-TNT)

Recruiting now · Phase 2

Conditions studied: Rectal Malignant Neoplasms

In brief

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.

Key facts

Study ID: NCT07026422
Run by: Shandong Cancer Hospital and Institute
People needed: 54
Starts: 2025-04-30
Expected to finish: 2028-05-30
Last updated by the study team: 2026-05-18

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Age 18-75 years old, male and female
Histologically confirmed pMMR/MSS rectal adenocarcinoma, defined by MRI as clinical stage II (T3-4, N-) or stage III (any T, N+)
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)
Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
No evidence of distant metastases based on chest and abdominal CT or whole body PET-CT examinations
No other rectal cancer (e.g., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, neuroendocrine carcinoma, etc.) or synchronous colon cancer
Presence of measurable lesions that meet RECIST v1.1 criteria for evaluation.

You may not qualify if…

dMMR or MSI-H patients
Myelosuppression without obvious causes
Locally advanced rectal cancer without high-risk factors
Prior or concurrent other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix)
Severe allergic reaction to other monoclonal antibodies
Uncontrolled cardiac clinical symptoms or disease
Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
Abnormal coagulation (INR>1.5 or PT>16s), bleeding tendency or on thrombolytic or anticoagulant therapy
Known history and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonitis, or severely impaired lung function
Known history of prior antitumor therapy, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T-cell related therapy, etc.
Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1-2 antibody-positive), active syphilis infection, active tuberculosis infection, or active hepatitis B virus or hepatitis C virus infection at screening

Where it is running

Shandong Cancer Hospital and Institute — Jinan, Shandong, China (enrolling)

Full record on ClinicalTrials.gov

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