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

Launched by SHANDONG CANCER HOSPITAL AND INSTITUTE · Jun 16, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment approach for people with a certain type of rectal cancer called pMMR/MSS locally advanced rectal cancer. This form of cancer usually doesn’t respond well to current immunotherapy medicines, which work better in other types of colorectal cancer. The study is exploring whether combining immunotherapy drugs (iparomlimab and tuvonralimab) with standard treatments like chemotherapy and radiation before surgery can improve outcomes. The goal is to see if this combination helps the immune system better attack the cancer and makes the treatment more effective and safe.

To take part, patients need to be between 18 and 75 years old with confirmed pMMR/MSS rectal cancer that is locally advanced but hasn’t spread to other parts of the body. The tumor must be located within 12 cm of the anus and have certain high-risk features identified by imaging tests. Participants should be in good overall health and have not received prior cancer treatments for this condition. During the trial, patients will receive a combination of immunotherapy, chemotherapy, and radiation before surgery, and doctors will closely monitor their response and any side effects. This study is currently recruiting eligible patients and aims to offer a promising new option for those with this challenging type of rectal cancer.

Gender

ALL

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 cancer without high-risk factors
• • 4. Prior or concurrent other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix)
• • 5. Severe allergic reaction to other monoclonal antibodies
• • 6. Uncontrolled cardiac clinical symptoms or disease
• • 7. Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
• • 8. Abnormal coagulation (INR\>1.5 or PT\>16s), bleeding tendency or on thrombolytic or anticoagulant therapy
• • 9. Known history and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonitis, or severely impaired lung function
• • 10. Known history of prior antitumor therapy, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T-cell related therapy, etc.
• • 11. 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