dMMR/MSI-H-type Rectal AdenocarcinomaPhase 2Neo-ITNCT07160647
The Efficacy and Safety of Neoadjuvant Therapy With Iparomlimab and Tuvonralimab in Locally Advanced MSI-H/dMMR Colorectal Cancer: An Prospective, Single-Arm Study (Neo-IT)
A Phase 2 study testing Ipalolimab and Tovorilimab in people with dMMR/MSI-H-type Rectal Adenocarcinoma, run by Sir Run Run Shaw Hospital at 1 site in China.
Trial summary
Immunotherapy may bring revolutionary changes to the preoperative neoadjuvant treatment mode for dMMR/MSI-H locally advanced rectal cancer. According to the existing theory, the use of Iparomlimab and Tuvonralimab may be the best solution. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- dMMR/MSI-H-type Rectal Adenocarcinoma
- What is being tested?
- Ipalolimab and Tovorilimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteChina
- Study dates
- 20 Aug 2025to 30 Aug 2030
- 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
- Patients willing to receive neoadjuvant therapy.
- Age ≥18 years.
- Histologically confirmed primary colorectal adenocarcinoma (without squamous or sarcomatoid components).
- Radiologically assessed (contrast-enhanced CT or MRI) as surgically resectable stage IIB-III (limited to cT4 or cN+ per AJCC 8th edition).
- Confirmed dMMR or MSI-H status by immunohistochemistry or MSI genetic testing.
- Lesions diagnosed by investigators as amenable to radical resection (R0 resection) without requiring multi-organ resection prior to neoadjuvant therapy.
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- Voluntary participation with signed informed consent.
- ECOG performance status score of 0-1.
- No prior antitumor or immunotherapy before enrollment.
- Adequate organ and bone marrow function defined as:
- Hematology: Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L; Platelets (PLT) ≥100×10⁹/L; Hemoglobin (HGB) ≥7.0 g/dL.
- Liver function: Total Bilirubin (TBIL) ≤1.5×ULN; Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) ≤3×ULN; Serum Albumin (ALB) ≥28 g/L.
- Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min; Urine dipstick shows protein <2+; for subjects with baseline urine dipstick protein ≥2+, a 24-hour urine collection must demonstrate protein <1 g.
- Coagulation: International Normalized Ratio (INR) ≤1.5 and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN.
- No severe comorbidities jeopardizing survival (life expectancy <5 years).
- Fertile female subjects or male subjects with fertile partners must use effective contraception during and for 6 months after treatment. Postmenopausal status or negative urine/serum pregnancy test for premenopausal females.
Who cannot join
- 1.Prior antitumor therapy for the disease under investigation, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
- 2.Previous treatment with anti-PD-1, anti-PD-L1, anti-programmed death ligand 2 (PD-L2), or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agents, or any other drugs targeting T-cell co-stimulation or immune checkpoint pathways (e.g., OX40, CD137), as well as adoptive cell immunotherapy.
- 3.Concurrent participation in another interventional clinical study. 4.Treatment with any investigational drug or device within 4 weeks prior to the first dose of the study drug.
- 5.Within 7 days before screening laboratory tests: receipt of blood transfusion, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), thrombopoietin (TPO), or IL-11 therapy.
- 6.Use of immunosuppressive drugs within 4 weeks before the first dose of the study drug, excluding: intranasal/inhaled topical steroids or local steroid injections (e.g., intra-articular); systemic corticosteroids at doses ≤10 mg/day prednisone or equivalent; corticosteroids as premedication for allergic reactions (e.g., CT scan premedication).
- 7.Use of Chinese herbal medicine with antitumor indications or immunomodulatory drugs (including thymosin, interferon, interleukin, etc.) within 1 week before the first dose of the study drug.
- 8.Receipt of live or attenuated vaccines within 4 weeks before the first dose or anticipated during the study.
- 9.Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose, anticipated need for major surgery during the study (except protocol-defined radical resection for colon cancer), or presence of unhealed wounds, ulcers, or fractures.
Trial locations and contacts
1 site in 1 country.
China1 site
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine,
Hangzhou, Zhejiang, 310016
About this study
Immunotherapy may bring revolutionary changes to the preoperative neoadjuvant treatment mode for dMMR/MSI-H locally advanced rectal cancer. According to the existing theory, the use of Iparomlimab and Tuvonralimab may be the best solution. In this study, the investigators will perform single-cell sequencing of participants tissue samples, fully explore the multi-dimensional omics information of tumors and microenvironments, explore the characteristics of the treatment benefit population, and try to construct an efficacy prediction model to screen the treatment benefit population early and implement precise treatment.
- Conditions
- dMMR/MSI-H-type Rectal Adenocarcinoma
- Being tested
- Ipalolimab and Tovorilimab
- Keywords
- Iparomlimab and Tuvonralimab, MSI-H, dMMR, Rectal Adenocarcinoma
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ipalolimab and TovorilimabDrug
1.Active Ingredients: Ipalolimab and Tovorilimab (a dual-functional combination antibody consisting of Ipalolimab, a recombinant humanized monoclonal antibody targeting programmed death receptor-1 [PD-1], and Tovorilimab, a recombinant humanized monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein-4 [CTLA-4]). 2.Specification: 50 mg (2 mL) per vial. 3.Dosage and Administration: Administer via intravenous infusion at a recommended dose of 5 mg/kg every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| a combined treatment regimen of immunotherapy and radical surgical resection | Experimental | Eligible patients with advanced MSI-H/dMMR colorectal cancer will receive a combined treatment regimen of immunotherapy and radical surgical resection. The specific procedures are as follows:
Anti-PD-1/CTLA-4 dual immunotherapy (5 mg/kg, IV, D1, Q3W, 4 cycles). Radical surgical resection will be performed after the completion of immunotherapy. Receives: Drug: Ipalolimab and Tovorilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of the study is to evaluate the pathologic complete response (pCR) rate
Description: pCR was defined as the absence of viable tumour cells in the resected primary tumour specimen and all sampled regional lymph nodes (ypT0N0).
Measured: Up to 13 weeks (once surgery is done)
Secondary outcomes (5)
Tumor regression grade
Tumor Regression Grade（TRG）will be done via pathologic assessment on the surgical specimen with AJCC/CAP TRG system
Measured: Up to 13 weeks (once surgery is done)
The proportion of participants who remain survival at 3 years
Defined as the percentage of patients alive after 3-year follow-up
Measured: Up to 3 years
The proportion of participants who remain progression free at 3 years
Defined as the percentage of patients without disease recurrence or progression after 3-year follow-up
Measured: Up to 3 years
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Treatment- related adverse events are assessed by NCI-CTCAE v5.0 in each visit
Measured: Up to 3 years
Quality of life of the patients
Quality of life is measured via FACT-C questionnaire in each visit.
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2025
- Study start20 Aug 2025
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for dMMR/MSI-H-type Rectal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Sir Run Run Shaw HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sir Run Run Shaw Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sheng Dai, Sir Run Run Shaw Hospital
- Investigators
- Xiujun Cai, MD, Study chair, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07160647
- Sponsor's protocol ID
- SRRSH2025-0483
- Acronym
- Neo-IT
- Status last verified
- Nov 2025
- First submitted
- 25 Aug 2025
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Neoadjuvant Therapy With Iparomlimab and Tuvonralimab in Locally Advanced MSI-H/dMMR Colorectal Cancer: An Prospective, Single-Arm Study (Neo-IT)
- ClinicalTrials.gov ID
- NCT07160647
- Acronym / sponsor ID
- Neo-IT / SRRSH2025-0483
- Conditions
- dMMR/MSI-H-type Rectal Adenocarcinoma
- Keywords
- Iparomlimab and Tuvonralimab, MSI-H, dMMR, Rectal Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Sir Run Run Shaw HospitalUniversity, hospital or other
- Study start
- 20 Aug 2025 (actual)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 30 Aug 2030 (estimated)
- First posted
- 8 Sep 2025 (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.
Immunotherapy may bring revolutionary changes to the preoperative neoadjuvant treatment mode for dMMR/MSI-H locally advanced rectal cancer. According to the existing theory, the use of Iparomlimab and Tuvonralimab may be the best solution. In this study, the investigators will perform single-cell sequencing of participants tissue samples, fully explore the multi-dimensional omics information of tumors and microenvironments, explore the characteristics of the treatment benefit population, and try to construct an efficacy prediction model to screen the treatment benefit population early and implement precise treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| a combined treatment regimen of immunotherapy and radical surgical resection | Experimental | Drug: Ipalolimab and TovorilimabEligible patients with advanced MSI-H/dMMR colorectal cancer will receive a combined treatment regimen of immunotherapy and radical surgical resection. The specific procedures are as follows: Anti-PD-1/CTLA-4 dual immunotherapy (5 mg/kg, IV, D1, Q3W, 4 cycles). Radical surgical resection will be performed after the completion of immunotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients willing to receive neoadjuvant therapy.
- Age ≥18 years.
- Histologically confirmed primary colorectal adenocarcinoma (without squamous or sarcomatoid components).
- Radiologically assessed (contrast-enhanced CT or MRI) as surgically resectable stage IIB-III (limited to cT4 or cN+ per AJCC 8th edition).
- Confirmed dMMR or MSI-H status by immunohistochemistry or MSI genetic testing.
Key exclusion criteria (8 listed)
- 1.Prior antitumor therapy for the disease under investigation, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
- 2.Previous treatment with anti-PD-1, anti-PD-L1, anti-programmed death ligand 2 (PD-L2), or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agents, or any other drugs targeting T-cell co-stimulation or immune checkpoint pathways (e.g., OX40, CD137), as well as adoptive cell immunotherapy.
- 3.Concurrent participation in another interventional clinical study. 4.Treatment with any investigational drug or device within 4 weeks prior to the first dose of the study drug.
- 5.Within 7 days before screening laboratory tests: receipt of blood transfusion, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), thrombopoietin (TPO), or IL-11 therapy.
- 6.Use of immunosuppressive drugs within 4 weeks before the first dose of the study drug, excluding: intranasal/inhaled topical steroids or local steroid injections (e.g., intra-articular); systemic corticosteroids at doses ≤10 mg/day prednisone or equivalent; corticosteroids as premedication for allergic reactions (e.g., CT scan premedication).
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 |
|---|---|---|
| Ipalolimab and Tovorilimab1.Active Ingredients: Ipalolimab and Tovorilimab (a dual-functional combination antibody consisting of Ipalolimab, a recombinant humanized monoclonal antibody targeting programmed death receptor-1 [PD-1], and Tovorilimab, a recombinant humanized monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein-4 [CTLA-4]). 2.Specification: 50 mg (2 mL) per vial. 3.Dosage and Administration: Administer via intravenous infusion at a recommended dose of 5 mg/kg every 3 weeks. | Drug | a combined treatment regimen of immunotherapy and radical surgical resection |
Primary outcome
The primary objective of the study is to evaluate the pathologic complete response (pCR) rate
Time frame: Up to 13 weeks (once surgery is done)
Description: pCR was defined as the absence of viable tumour cells in the resected primary tumour specimen and all sampled regional lymph nodes (ypT0N0).
5 secondary outcomes
Tumor regression grade
Time frame: Up to 13 weeks (once surgery is done)
The proportion of participants who remain survival at 3 years
Time frame: Up to 3 years
The proportion of participants who remain progression free at 3 years
Time frame: Up to 3 years
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Time frame: Up to 3 years
Quality of life of the patients
Time frame: up to 3 years
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 2 Dec 2025.
- Individual participant dataSharing planned: Undecided
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. This study is not recruiting at the moment.
Xiujun Cai, MD study chair
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016
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 Ipalolimab and Tovorilimab in people with dMMR/MSI-H-type Rectal Adenocarcinoma, run by Sir Run Run Shaw Hospital 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 16 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 2 Dec 2025. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective of the study is to evaluate the pathologic complete response (pCR) rate (time frame: Up to 13 weeks (once surgery is done)). 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 2 Dec 2025; AzTrials last refreshed its copy on 8 Nov 2026.