Colorectal Cancer (MSI-H)Phase 2TORCH-OPTIMANCT07403877
Neoadjuvant Immunotherapy ± Radiotherapy in MSI-H/dMMR Locally Advanced Colorectal Cancer
A Phase 2 study testing Nivolumab, Ipilimumab (1mg/kg) and PULSAR in people with Colorectal Cancer (MSI-H), run by Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer (MSI-H)
- What is being tested?
- Nivolumab, Ipilimumab (1mg/kg) and PULSAR
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2026to 31 Dec 2034
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathologically confirmed primary colorectal adenocarcinoma.
- Radiographic assessment showed a stage II-III based on AJCC Stage 8th ed.
- At least 18 years old.
- MSI-H or dMMR.
- The Eastern Cooperative Oncology Group performance status (ECOG PS) score is 0 or 1.
- Physical state or organ function can tolerate the planned treatment of the study protocol.
- Agreed to sign written informed consent before recruitment.
Who cannot join
- Previously received any antitumor therapy for the disease under study, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
- Pregnancy or breastfeeding women.
- History of other malignancies within 5 years.
- Serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
- Immunodeficiency disease or long-term using of immunosuppressive agents.
- Allergic to any component of the therapy.
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- Any other condition or disease that is not suitable to take the therapy included in the protocol.
- Concurrent participation in another clinical study, unless participating in an observational (non-interventional) clinical study or in the survival follow-up phase of an interventional study.
- Received any investigational drug or device treatment within 4 weeks prior to initial administration of the investigational drug.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Fudan University Shanghai Cancer Center
Shanghai
Menglong Zhou, MD, 86-18121299608, mrzhouml@163.com
Sanjun Cai, MD
About this study
Official title: A Phase II Randomized Controlled Trial of Neoadjuvant Immunotherapy With or Without Radiotherapy in Locally Advanced Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Cancer
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)
- Being tested
- Nivolumab, Ipilimumab (1mg/kg), PULSAR, Radical surgery, Watch & wait
- Keywords
- colorectal cancer, microsatellite instability high, mismatch repair-deficient, neoadjuvant therapy, radiotherapy, immunotherapy, locally advanced
- Medical subject headings
- Colorectal Neoplasms, Turcot syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Nivolumab 240 mg every 2 weeks
Ipilimumab (1mg/kg)Drug
Ipilimumab 1 mg/kg every 3 weeks
PULSARRadiation
Irradiation targeted to the primary lesion (5 Gy per fraction, total 4 fractions, delivered every 3 weeks).
Radical surgeryProcedure or surgery
Surgical resection will be performed in resectable cases.
Watch & waitOther
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 group | Role | What they receive |
|---|---|---|
| anti-PD-1 plus anti-CTLA-4 | Experimental | Arm A: Nivolumab 240 mg every 2 weeks (6 doses) plus ipilimumab 1 mg/kg every 3 weeks (4 doses). Receives: Drug: Nivolumab; Drug: Ipilimumab (1mg/kg); Procedure: Radical surgery; Other: Watch & wait |
| anti-PD-1 plus radiotherapy | Experimental | 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). Receives: Drug: Nivolumab; Radiation: PULSAR; Procedure: Radical surgery; Other: Watch & wait |
| anti-PD-1 monotherapy | Active comparator | Arm C: Nivolumab 240 mg every 2 weeks (6 doses). Receives: Drug: Nivolumab; Procedure: Radical surgery; Other: Watch & wait |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete regression (CR) rate
Proportion of patients achieving either clinical CR (and undergoing WW) or pathological CR (confirmed by pathology) among all evaluable patients.
Measured: 1 month after surgery or the completion of neoadjuvant therapy
Secondary outcomes (7)
R0 resection rate
Proportion of patients who achieve R0 resection.
Measured: 1 month after surgery
Objective response rate (ORR)
Proportion of patients with complete response (CR) or partial response (PR) to preoperative multimodal therapy. ORR will be evaluated using RESIST1.1 by CT/MRI of the chest, abdomen, and pelvis.
Measured: 6 months after the enrollment of the last subject
Event-free survival (EFS)
The EFS was defined as the time from randomization to the first determination of inoperable disease progression, postoperative local recurrence or distant metastasis, tumor regrowth, or death from any cause, whichever occurs first.
Measured: 36 months after the enrollment of the last subject
Overall survival (OS)
OS is defined as the time interval from enrollment to death of any reason or censoring.
Measured: 36 months after the enrollment of the last subject
Toxicities
Number of participants with treatment-related adverse events (TrAEs) reported between the first dose and 28 days after the last dose of study therapy as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Measured: From the time of enrollment, assessed up to 28 days after the last dose of study therapy
Surgical morbidity
Surgery related adverse events (SRAEs) refer to complications which happen during or one month after surgery. Severe complications after surgery will be documented and classified by Clavien-Dindo classification, such as abdominal or GI tract bleeding, anastomotic fistula, pancreatic fistula of grade B or above, and incision complications (infection, bleeding, rupture).
Measured: During or one month after surgery
Surgical mortality
Death from any cause within 30 days of the date of surgery will be considered a surgical mortality death.
Measured: During or one month after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start1 Feb 2026 (estimated)
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer (MSI-H)Studies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhen Zhang, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07403877
- Sponsor's protocol ID
- FDRT-2025-592-4741
- Acronym
- TORCH-OPTIMA
- Status last verified
- Nov 2025
- First submitted
- 1 Feb 2026
- Last updated
- 11 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Controlled Trial of Neoadjuvant Immunotherapy With or Without Radiotherapy in Locally Advanced Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07403877
- Acronym / sponsor ID
- TORCH-OPTIMA / FDRT-2025-592-4741
- Conditions
- Colorectal Cancer (MSI-H)
- Keywords
- colorectal cancer, microsatellite instability high, mismatch repair-deficient, neoadjuvant therapy, radiotherapy, immunotherapy, locally advanced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Feb 2026 (estimated)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2034 (estimated)
- First posted
- 11 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| anti-PD-1 plus anti-CTLA-4 | Experimental | Drug: Nivolumab, Drug: Ipilimumab (1mg/kg), Procedure: Radical surgery, Other: Watch & waitArm A: Nivolumab 240 mg every 2 weeks (6 doses) plus ipilimumab 1 mg/kg every 3 weeks (4 doses). |
| anti-PD-1 plus radiotherapy | Experimental | Drug: Nivolumab, Radiation: PULSAR, Procedure: Radical surgery, Other: Watch & waitArm 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). |
| anti-PD-1 monotherapy | Active comparator | Drug: Nivolumab, Procedure: Radical surgery, Other: Watch & waitArm C: Nivolumab 240 mg every 2 weeks (6 doses). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histopathologically confirmed primary colorectal adenocarcinoma.
- Radiographic assessment showed a stage II-III based on AJCC Stage 8th ed.
- At least 18 years old.
- MSI-H or dMMR.
- The Eastern Cooperative Oncology Group performance status (ECOG PS) score is 0 or 1.
Key exclusion criteria (9 listed)
- Previously received any antitumor therapy for the disease under study, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
- Pregnancy or breastfeeding women.
- History of other malignancies within 5 years.
- Serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
- Immunodeficiency disease or long-term using of immunosuppressive agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabNivolumab 240 mg every 2 weeks | Drug | anti-PD-1 monotherapy, anti-PD-1 plus anti-CTLA-4, anti-PD-1 plus radiotherapy |
| Ipilimumab (1mg/kg)Ipilimumab 1 mg/kg every 3 weeks | Drug | anti-PD-1 plus anti-CTLA-4 |
| PULSARIrradiation targeted to the primary lesion (5 Gy per fraction, total 4 fractions, delivered every 3 weeks). | Radiation | anti-PD-1 plus radiotherapy |
| Radical surgerySurgical resection will be performed in resectable cases. | Procedure or surgery | anti-PD-1 monotherapy, anti-PD-1 plus anti-CTLA-4, anti-PD-1 plus radiotherapy |
| Watch & waitFor 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. | Other | anti-PD-1 monotherapy, anti-PD-1 plus anti-CTLA-4, anti-PD-1 plus radiotherapy |
Primary outcome
Complete regression (CR) rate
Time frame: 1 month after surgery or the completion of neoadjuvant therapy
Proportion of patients achieving either clinical CR (and undergoing WW) or pathological CR (confirmed by pathology) among all evaluable patients.
7 secondary outcomes
R0 resection rate
Time frame: 1 month after surgery
Objective response rate (ORR)
Time frame: 6 months after the enrollment of the last subject
Event-free survival (EFS)
Time frame: 36 months after the enrollment of the last subject
Overall survival (OS)
Time frame: 36 months after the enrollment of the last subject
Toxicities
Time frame: From the time of enrollment, assessed up to 28 days after the last dose of study therapy
Surgical morbidity
Time frame: During or one month after surgery
Surgical mortality
Time frame: During or one month after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Ipilimumab (1mg/kg) and PULSAR in people with Colorectal Cancer (MSI-H), run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Menglong Zhou, MD (86+18121299608, mrzhouml@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete regression (CR) rate (time frame: 1 month after surgery or the completion of neoadjuvant therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2026.