NCT06864013

SCRT Combined With Chemotherapy and Iparomlimab and Tuvonralimab in MSS or pMMR Patients With Locally Advanced Rectal Cancer

Short-course Neoadjuvant Radiotherapy Combined With Chemotherapy and Iparomlimab and Tuvonralimab in Microsatellite Stability (MSS) or Mismatch-repair-proficient (pMMR) Patients With Locally Advanced Rectal Cancer: A Randomized Controlled Clinical Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 116 (estimated)
• Sponsor: First Affiliated Hospital of Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Colorectal cancer ranks as the third most prevalent malignancy worldwide and the second leading cause of cancer-related mortality. For patients with locally advanced rectal cancer (LARC) classified as T3-4/N+ without distant metastasis, achieving organ preservation and functional integrity while pursuing curative treatment remains a formidable clinical challenge. This study aims to evaluate the efficacy and organ preservation rates of a novel neoadjuvant regimen comprising short-course radiotherapy followed by four cycles of CAPEOX combined with Iparomlimab and Tuvonralimab in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) LARC. Furthermore, the project will investigate potential predictive biomarkers for complete response (CR) within this immunotherapy-based total neoadjuvant therapy (iTNT) paradigm.

Detailed description

This study adopts a prospective, multicenter research design. It aims to evaluate the effectiveness and organ preservation rate of neoadjuvant short-course radiotherapy followed by 4 cycles of CAPEOX + Iparomlimab and Tuvonralimab in patients with MSS or pMMR LARC (AJCC eighth edition stage cT3-4 / cN+) who are initially diagnosed and can be surgically resected and randomized to the experimental group (SCRT followed by 4 cycles of CAPEOX combined with Iparomlimab and Tuvonralimab) and the control group (SCRT followed by 4 cycles of CAPEOX). The experimental group will receive neoadjuvant short-course radiotherapy, followed by CAPEOX+Iparomlimab and Tuvonralimab for 4 cycles. The control group will receive neoadjuvant short-course radiotherapy,followed by CAPEOX for 4 cycles. During or after the completion of neoadjuvant therapy, if the patients cannot undergo radical surgical resection due to disease progression (based on RECIST v1.1) or other reasons, the treatment of this study will be terminated. For patients who are evaluated as clinical complete remission (cCR) by imaging, colonoscopy, and pathology, the watch and wait (W\&W) indications or surgical methods will be discussed by multidisciplinary team (MDT). Among them, patients with cCR or near clinical complete remission (ncCR) in efficacy evaluation will receive W\&W or transanal endoscopic surgery (TES) to preserve organ function, and patients with non-cCR/ncCR will undergo total mesorectal excision (TME). After surgery, patients in the experimental group will receive CAPEOX combined with Iparomlimab and Tuvonralimab for 4 cycles, followed by sequential treatment with Iparomlimab and Tuvonralimab for up to 1 year. Patients in the control group will receive CAPEOX for 4 cycles until the planned course of treatment is completed or the disease relapses, intolerable toxicity occurs, informed consent is withdrawn, lost to follow-up or death, or other circumstances that require treatment discontinuation (whichever occurs first).

Conditions

• Locally Advanced Rectal Cancer (LARC)

Interventions

Type	Name	Description
DRUG	Experimental	The experimental group will receive neoadjuvant short-course radiotherapy (dose 25Gy/5f), followed by CAPEOX+Iparomlimab and Tuvonralimab (capecitabine 1000mg/m2 bid po d1-d14, q3w; oxaliplatin 130mg/m2 iv d1, q3w; Iparomlimab and Tuvonralimab 5mg/kg iv d1, q3w) for 4 cycles. Patients who undergo surgery will receive CAPEOX combined with Iparomlimab and Tuvonralimab for 4 cycles, followed by sequential treatment with Iparomlimab and Tuvonralimab for up to 1 year.
DRUG	Control	The control group will receive neoadjuvant short-course radiotherapy,followed by CAPEOX (capecitabine 1000mg/m2 bid po d1-d14, q3w; oxaliplatin 130mg/m2 iv d1, q3w) for 4 cycles. Patients who undergo sugery will receive CAPEOX for 4 cycles.

Timeline

• Start date: 2025-01-06
• Primary completion: 2029-12-31
• Completion: 2029-12-31
• First posted: 2025-03-07
• Last updated: 2026-01-14

Locations

1 site across 1 country: China