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

Sponsor
Fudan University
Study ID
NCT07403877
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

  • Colorectal Cancer (MSI-H)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    Nivolumab 240 mg every 2 weeks
  • Ipilimumab (1mg/kg) — DRUG
    Ipilimumab 1 mg/kg every 3 weeks
  • PULSAR — RADIATION
    Irradiation targeted to the primary lesion (5 Gy per fraction, total 4 fractions, delivered every 3 weeks).
  • Radical surgery — PROCEDURE
    Surgical resection will be performed in resectable cases.
  • Watch & wait — OTHER
    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.

Study Details

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.

Key Dates

Start date
Feb 1, 2026
Status verified
Nov 2025
Primary completion
Dec 31, 2031
Completion
Dec 31, 2034

Study Design

Enrollment
114 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: anti-PD-1 plus anti-CTLA-4
    Arm A: Nivolumab 240 mg every 2 weeks (6 doses) plus ipilimumab 1 mg/kg every 3 weeks (4 doses).
  • Experimental: anti-PD-1 plus radiotherapy
    Arm B: Radiotherapy (5 Gy per fraction, total 4 fractions, delivered every 3 weeks) to the primary lesion plus nivolumab 240 mg every 2 weeks (6 doses).
  • Active Comparator: anti-PD-1 monotherapy
    Arm C: Nivolumab 240 mg every 2 weeks (6 doses).

Primary Outcome Measure

Complete regression (CR) rate [ Time Frame: 1 month after surgery or the completion of neoadjuvant therapy ]

Central Contacts

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