Iparomlimab and tuvonralimab added to total neoadjuvant therapy for pMMR/MSS locally advanced rectal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2 interventional trial enrolls patients with pMMR/MSS locally advanced rectal adenocarcinoma and integrates dual immune checkpoint blockade (iparomlimab/tuvonralimab) into a total neoadjuvant therapy (TNT) backbone that includes chemoradiotherapy (CRT), surgery (total mesorectal excision), and adjuvant chemotherapy. The regimen uses a "sandwich" or TNT approach to deliver systemic chemotherapy and CRT in a sequence intended to increase pathological complete response (pCR) rates and reduce distant recurrence. Immune checkpoint inhibitors are given alongside CRT to try to convert an immune-cold tumor microenvironment into a more responsive one for pMMR/MSS tumors. The trial will monitor tumor response, safety, and surgical outcomes at a single center in Jinan, Shandong.

Why it matters

Who can join: the full rules

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

Where it's running

• Shandong Cancer Hospital and Institute
  Jinan, Shandong, China Recruiting

Study contacts

• Principal investigator: Jinbo Yue, Docter — Shandong Cancer Hospital and Institute, Department of Radiation Oncology
• Study coordinator: Jinbo Yue, Docter
• Email: jbyue@sdfmu.edu.cn
• Phone: 0531-67626441

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Iparomlimab and Tuvonralimab With Cetuximab Before Surgery in Resectable Oral Cancer

  In this phase 2 study, patients with locally advanced, resectable oral squamous cell carcinoma will receive a combination of iparomlimab, tuvonralimab, and cetuximab before surgery to see if the treatment is safe and can shrink tumors.

  Recruiting Phase 2 Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University · Shanghai, Shanghai Municipality · NCT07882888

• Iparomlimab/Tuvonralimab with nab-paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer

  This trial tests whether adding Iparomlimab/Tuvonralimab to nab-paclitaxel and cisplatin before surgery can shrink locally advanced cervical cancer and safely be given to adult women.

  Recruiting Phase 2 Xijing Hospital · Xi'an, Shaanxi · NCT07876154

• Neoadjuvant immunotherapy plus Nab-P-SOX for locally advanced gastric/GEJ cancer

  This phase 2, single-arm study tests a pre-surgery treatment that combines a PD-1/CTLA-4 bispecific antibody with nab-paclitaxel, oxaliplatin, and S-1 in adults with HER2-negative, locally advanced gastric or GEJ cancer.

  Recruiting Phase 2 Ruijin Hospital · Shanghai, Shanghai Municipality · NCT07867392

• Cryoablation with liver-directed immunotherapy and targeted therapy for melanoma liver metastases

  This trial tests a combination therapy including cryoablation, hepatic artery delivery of QL1706, intravenous dacarbazine, and oral lenvatinib to treat liver metastases from malignant melanoma in adults.

  Recruiting Phase 2 Sun Yat-sen University · Guangzhou, Guangdong · NCT07847359

• HAIC plus QL1706 and bevacizumab as first-line therapy for unresectable HER2-negative intrahepatic cholangiocarcinoma

  This study tests a liver-directed chemotherapy plus immune therapy and a blood vessel blocker to see if it helps people with unresectable intrahepatic cholangiocarcinoma.

  Recruiting Phase 2 Sun Yat-sen University · Guangzhou, Guangdong · NCT07841574

• Iparomlimab and Tuvonralimab with SBRT and Lenvatinib for Potentially Resectable Intermediate-Stage HCC

  This trial tests whether adding two antibodies together with SBRT and lenvatinib can improve outcomes for adults with potentially resectable intermediate-stage hepatocellular carcinoma.

  Recruiting Phase 2 Tianjin Medical University Cancer Institute and Hospital · Tianjin · NCT07801287

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.