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

NCT07026422 | Recruiting Phase 2

• 1 other identifier: SDZLEC2025-151-02
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Malignant Neoplasms

Outcome Measures

Primary Outcomes (1)

• Overall complete response (CR) rate

  Overall complete response (CR) rate, meaning the rates of pathological complete response (pCR) plus clinical complete response (cCR).

  1 year

Secondary Outcomes (6)

• Overall survival (OS)

  3 year

• Rate of surgical complications

  1 year

• Organ preservation rate

  1 year

• 3 year disease free survival (DFS) rate

  3 year

• 3 year local recurrence free survival (LRFS) rate

  3 year

Study Arms (1)

Dual immunotherapy group

EXPERIMENTAL

Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy

Combination Product: Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy

Interventions

Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy COMBINATION_PRODUCT

1. Radiotherapy: Radiotherapy location: primary site and the corresponding draining lymph node. Radiotherapy techniques: IMRT/VMRT. Radiotherapy dose and fractionation pattern: conventional external irradiation, 50Gy/25 fx/5 weeks or 25Gy/5fx/1 week. 2. Chemotherapy: Long-course radiotherapy concurrent with chemotherapy: capecitabine 825mg/m2, bid, d1-5/week. Short-course radiotherapy without concurrent chemotherapy. Consolidation chemotherapy and immunotherapy: QL1706 (iparomlimab and tuvonralimab 5mg/kg, d1) and CAPOX (Oxaliplatin 130mg/m2, d1 + capecitabine 1000mg/m2, bid, d1-14), repeated on a 21-day cycle, for 6 cycles. 3. Surgery or watch-and-wait Total mesorectal excision (TME), or watch-and-wait (for patients with clinical complete response).

Dual immunotherapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, 250000, China

RECRUITING

Related Publications (1)

• Zhu Z, Zhang X, Yun Z, Wang C, Li W, Ma L, Xu L, Sun Y, Yu J, Yue J. [18F] AlF-NOTA-FAPI-04 PET/CT scans can predict pathologic complete response in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Radiother Oncol. 2026 Apr;217:111429. doi: 10.1016/j.radonc.2026.111429. Epub 2026 Feb 5.

  PMID: 41654222 DERIVED

MeSH Terms

Interventions

Chemoradiotherapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Jinbo Yue, Docter

  Shandong Cancer Hospital and Institute, Department of Radiation Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinbo Yue, Docter

CONTACT

0531-67626441; jbyue@sdfmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Radiation Oncology Department

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: June 18, 2025
• Study Start: April 30, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): May 30, 2028
• Last Updated: May 18, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)