NCT07403877

Neoadjuvant Immunotherapy ± Radiotherapy in MSI-H/dMMR Locally Advanced Colorectal Cancer

A Phase II Randomized Controlled Trial of Neoadjuvant Immunotherapy With or Without Radiotherapy in Locally Advanced Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 114 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II clinical trial evaluates the efficacy and safety of three neoadjuvant regimens in patients with locally advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC): 1) Regimen A: Dual immune checkpoint blockade with nivolumab plus ipilimumab. 2) Regimen B: Nivolumab plus radiotherapy. 3) Regimen C: Nivolumab monotherapy. The primary objectives are to determine whether: 1) Dual immune checkpoint blockade (Regimen A) is superior to nivolumab monotherapy (Regimen C); and 2) Immunotherapy plus radiotherapy (Regimen B) is superior to nivolumab monotherapy (Regimen C). Methods: Participants will be randomized in a 1:1:1 ratio to one of the three arms. For patients with resectable tumors, surgical resection will be performed. In patients with low rectal cancer and poor prospects for sphincter preservation, a watch-and-wait (WW) strategy is an option if a clinical complete response (CR) is achieved following neoadjuvant therapy.

Conditions

• Colorectal Cancer (MSI-H)

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab 240 mg every 2 weeks
DRUG	Ipilimumab (1mg/kg)	Ipilimumab 1 mg/kg every 3 weeks
RADIATION	PULSAR	Irradiation targeted to the primary lesion (5 Gy per fraction, total 4 fractions, delivered every 3 weeks).
PROCEDURE	Radical surgery	Surgical resection will be performed in resectable cases.
OTHER	Watch & wait	For patients with low rectal cancer who are unable to preserve the anal sphincter, a watch-and-wait (WW) strategy can be considered if a clinical complete response (CR) is achieved.

Timeline

• Start date: 2026-02-01
• Primary completion: 2031-12-31
• Completion: 2034-12-31
• First posted: 2026-02-11
• Last updated: 2026-02-11

Locations

1 site across 1 country: China