Rectal Malignant NeoplasmsPhase 2NCT07026422
Iparomlimab/Tuvonralimab Integrating With Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer (IT-TNT)
A Phase 2 study testing Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy in people with Rectal Malignant Neoplasms, run by Shandong Cancer Hospital and Institute at 1 site in China.
Trial summary
In colorectal cancer (CRC), ICIs show strong therapeutic associations with microsatellite instability-high (MSI-H) status, while patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors exhibit poor responses. Dual immunotherapy may represent a promising strategy for MSS populations. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Malignant Neoplasms
- What is being tested?
- Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2025to 30 May 2028
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years old, male and female
- Histologically confirmed pMMR/MSS rectal adenocarcinoma, defined by MRI as clinical stage II (T3-4, N-) or stage III (any T, N+)
- Tumor within 12 cm of the anal verge with at least one of the following high-risk factors: cT4, cN2, extramural vascular invasion [EMVI+], mesorectal fascia involved [MRF+], lateral lymph node [LN+], tumor deposit, or low rectal cancer (≤5 cm from the anal verge)
- Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
- No evidence of distant metastases based on chest and abdominal CT or whole body PET-CT examinations
- No other rectal cancer (e.g., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, neuroendocrine carcinoma, etc.) or synchronous colon cancer
- Presence of measurable lesions that meet RECIST v1.1 criteria for evaluation.
Who cannot join
- dMMR or MSI-H patients
- Myelosuppression without obvious causes
- Locally advanced rectal cancer without high-risk factors
- Prior or concurrent other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix)
- Severe allergic reaction to other monoclonal antibodies
- Uncontrolled cardiac clinical symptoms or disease
Show all 11Show fewer
- Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
- Abnormal coagulation (INR>1.5 or PT>16s), bleeding tendency or on thrombolytic or anticoagulant therapy
- Known history and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonitis, or severely impaired lung function
- Known history of prior antitumor therapy, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T-cell related therapy, etc.
- Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1-2 antibody-positive), active syphilis infection, active tuberculosis infection, or active hepatitis B virus or hepatitis C virus infection at screening
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, 1 recruiting
- Recruiting
Shandong Cancer Hospital and Institute
Jinan, Shandong, 250000
Jinbo Yue, 0531-67626441, jbyue@sdfmu.edu.cn
About this study
Official title: Iparomlimab/Tuvonralimab Integrating With Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer (IT-TNT): A Single-arm, Exploratory, Phase II Trial
In colorectal cancer (CRC), ICIs show strong therapeutic associations with microsatellite instability-high (MSI-H) status, while patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors exhibit poor responses. Dual immunotherapy may represent a promising strategy for MSS populations. The Dutch NICHE trial reported a 27% pathological response rate (4/15) in MSS CRC patients with clinical stage I-III disease treated with neoadjuvant ipilimumab plus nivolumab. In advanced or metastatic CRC, a study by Jin Li et al. demonstrated that iparomlimab/tuvonralimab combined with bevacizumab and the XELOX regimen achieved an objective response rate of 70.6% (95% CI: 56.2%-82.5%).
Radiotherapy may synergize with ICIs through multiple immunomodulatory mechanisms. For pMMR/MSS LARC, combining CRT with ICIs holds promise to overcome the "immune-cold" tumor microenvironment and improve therapeutic efficacy. In this clinical trial, the investigators aim to evaluate the efficacy and safety of integrating immunotherapy with CRT as a novel total neoadjuvant therapy for pMMR/MSS rectal cancer.
Read the detailed description
The "sandwich" approach, combining preoperative concurrent chemoradiotherapy (CRT) with total mesorectal excision (TME) and postoperative adjuvant chemotherapy, has been shown to improve pathological complete response (pCR) rates, local control rates (LCR), and sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, this strategy does not significantly enhance overall survival (OS) or distant metastasis-free survival (DMFS). Total neoadjuvant therapy (TNT), a novel treatment paradigm, involves administering chemotherapy either before neoadjuvant CRT (induction TNT) or after neoadjuvant CRT (consolidation TNT). This approach improves treatment compliance, reduces chemotherapy-related toxicity, and increases pCR rates. Patients achieving pCR following TNT exhibit lower risks of local tumor recurrence and improved survival outcomes.
Immune checkpoint inhibitors (ICIs) have become a cornerstone of cancer therapy. Antibodies targeting negative immune regulators-such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), and programmed cell death ligand 1 (PD-L1)-have demonstrated efficacy across multiple solid tumors. In colorectal cancer (CRC), ICIs show strong therapeutic associations with microsatellite instability-high (MSI-H) status, while patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors exhibit poor responses. Dual immunotherapy may represent a promising strategy for MSS populations. The Dutch NICHE trial reported a 27% pathological response rate (4/15) in MSS CRC patients with clinical stage I-III disease treated with neoadjuvant ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1), including 3 major pathological responses and 1 partial response. In advanced or metastatic CRC, a study by Jin Li et al. demonstrated that iparomlimab/tuvonralimab combined with bevacizumab and the XELOX regimen achieved an objective response rate of 70.6% (95% CI: 56.2%-82.5%).
Radiotherapy may synergize with ICIs through multiple immunomodulatory mechanisms, including enhanced tumor antigen release, activation of innate immune pathways, increased T-cell infiltration, improved antigen presentation, and modulation of immunosuppressive cells. For pMMR/MSS LARC, combining CRT with ICIs holds promise to overcome the "immune-cold" tumor microenvironment and improve therapeutic efficacy. In this clinical trial, the investigators aim to evaluate the efficacy and safety of integrating immunotherapy with CRT as a novel total neoadjuvant therapy for pMMR/MSS rectal cancer.
- Conditions
- Rectal Malignant Neoplasms
- Being tested
- Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapyCombination product
- Radiotherapy: Radiotherapy location: primary site and the corresponding draining lymph node. Radiotherapy techniques: IMRT/VMRT. Radiotherapy dose and fractionation pattern: conventional external irradiation, 50Gy/25 fx/5 weeks or 25Gy/5fx/1 week.
- Chemotherapy:
Long-course radiotherapy concurrent with chemotherapy: capecitabine 825mg/m2, bid, d1-5/week.
Short-course radiotherapy without concurrent chemotherapy. Consolidation chemotherapy and immunotherapy: QL1706 (iparomlimab and tuvonralimab 5mg/kg, d1) and CAPOX (Oxaliplatin 130mg/m2, d1 + capecitabine 1000mg/m2, bid, d1-14), repeated on a 21-day cycle, for 6 cycles. 3. Surgery or watch-and-wait Total mesorectal excision (TME), or watch-and-wait (for patients with clinical complete response).
| Study group | Role | What they receive |
|---|---|---|
| Dual immunotherapy group | Experimental | Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy Receives: Combination Product: Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall complete response (CR) rate
Overall complete response (CR) rate, meaning the rates of pathological complete response (pCR) plus clinical complete response (cCR).
Measured: 1 year
Secondary outcomes (6)
Overall survival (OS)
From date of radiotherapy initiation until the date of death from any cause or last follow-up, whichever came first.
Measured: 3 year
Rate of surgical complications
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Measured: 1 year
Organ preservation rate
Measured: 1 year
3 year disease free survival (DFS) rate
From date of surgery completion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Measured: 3 year
3 year local recurrence free survival (LRFS) rate
Time Frame: From date of surgery completion until the date of first documented pelvic failure, assessed up to 36 months
Measured: 3 year
The incidence and grade of adverse events
The incidence and grade of adverse events, determined according to NCI-CTCAE 5.0 criteria.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2025
- Study start30 Apr 2025
- Primary completion30 Nov 2026 (estimated)
- Study completion30 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal Malignant NeoplasmsStudies of the same condition, open and under way.
- 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
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong Cancer Hospital and Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinbo Yue, Shandong Cancer Hospital and Institute
- Investigators
- Jinbo Yue, Docter, Principal investigator, Shandong Cancer Hospital and Institute, Department of Radiation Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07026422
- Sponsor's protocol ID
- SDZLEC2025-151-03
- Status last verified
- Oct 2026
- First submitted
- 21 May 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhu Z, Zhang X, Yun Z, Wang C, Li W, Ma L, Xu L, Sun Y, Yu J, Yue J. [18F] AlF-NOTA-FAPI-04 PET/CT scans can predict pathologic complete response in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Radiother Oncol. 2026 Apr;217:111429. doi: 10.1016/j.radonc.2026.111429. Epub 2026 Feb 5.
PubMed 41654222
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Iparomlimab/Tuvonralimab Integrating With Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer (IT-TNT): A Single-arm, Exploratory, Phase II Trial
- ClinicalTrials.gov ID
- NCT07026422
- Acronym / sponsor ID
- SDZLEC2025-151-03
- Conditions
- Rectal Malignant Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Shandong Cancer Hospital and InstituteUniversity, hospital or other
- Study start
- 30 Apr 2025 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 May 2028 (estimated)
- First posted
- 18 Jun 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.
In colorectal cancer (CRC), ICIs show strong therapeutic associations with microsatellite instability-high (MSI-H) status, while patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors exhibit poor responses. Dual immunotherapy may represent a promising strategy for MSS populations. The Dutch NICHE trial reported a 27% pathological response rate (4/15) in MSS CRC patients with clinical stage I-III disease treated with neoadjuvant ipilimumab plus nivolumab. In advanced or metastatic CRC, a study by Jin Li et al. demonstrated that iparomlimab/tuvonralimab combined with bevacizumab and the XELOX regimen achieved an objective response rate of 70.6% (95% CI: 56.2%-82.5%).
Radiotherapy may synergize with ICIs through multiple immunomodulatory mechanisms. For pMMR/MSS LARC, combining CRT with ICIs holds promise to overcome the "immune-cold" tumor microenvironment and improve therapeutic efficacy. In this clinical trial, the investigators aim to evaluate the efficacy and safety of integrating immunotherapy with CRT as a novel total neoadjuvant therapy for pMMR/MSS rectal cancer.
Detailed description
The "sandwich" approach, combining preoperative concurrent chemoradiotherapy (CRT) with total mesorectal excision (TME) and postoperative adjuvant chemotherapy, has been shown to improve pathological complete response (pCR) rates, local control rates (LCR), and sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, this strategy does not significantly enhance overall survival (OS) or distant metastasis-free survival (DMFS). Total neoadjuvant therapy (TNT), a novel treatment paradigm, involves administering chemotherapy either before neoadjuvant CRT (induction TNT) or after neoadjuvant CRT (consolidation TNT). This approach improves treatment compliance, reduces chemotherapy-related toxicity, and increases pCR rates. Patients achieving pCR following TNT exhibit lower risks of local tumor recurrence and improved survival outcomes.
Immune checkpoint inhibitors (ICIs) have become a cornerstone of cancer therapy. Antibodies targeting negative immune regulators-such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), and programmed cell death ligand 1 (PD-L1)-have demonstrated efficacy across multiple solid tumors. In colorectal cancer (CRC), ICIs show strong therapeutic associations with microsatellite instability-high (MSI-H) status, while patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors exhibit poor responses. Dual immunotherapy may represent a promising strategy for MSS populations. The Dutch NICHE trial reported a 27% pathological response rate (4/15) in MSS CRC patients with clinical stage I-III disease treated with neoadjuvant ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1), including 3 major pathological responses and 1 partial response. In advanced or metastatic CRC, a study by Jin Li et al. demonstrated that iparomlimab/tuvonralimab combined with bevacizumab and the XELOX regimen achieved an objective response rate of 70.6% (95% CI: 56.2%-82.5%).
Radiotherapy may synergize with ICIs through multiple immunomodulatory mechanisms, including enhanced tumor antigen release, activation of innate immune pathways, increased T-cell infiltration, improved antigen presentation, and modulation of immunosuppressive cells. For pMMR/MSS LARC, combining CRT with ICIs holds promise to overcome the "immune-cold" tumor microenvironment and improve therapeutic efficacy. In this clinical trial, the investigators aim to evaluate the efficacy and safety of integrating immunotherapy with CRT as a novel total neoadjuvant therapy for pMMR/MSS rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dual immunotherapy group | Experimental | Combination Product: Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapyTotal neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 18-75 years old, male and female
- Histologically confirmed pMMR/MSS rectal adenocarcinoma, defined by MRI as clinical stage II (T3-4, N-) or stage III (any T, N+)
- Tumor within 12 cm of the anal verge with at least one of the following high-risk factors: cT4, cN2, extramural vascular invasion [EMVI+], mesorectal fascia involved [MRF+], lateral lymph node [LN+], tumor deposit, or low rectal cancer (≤5 cm from the anal verge)
- Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
- No evidence of distant metastases based on chest and abdominal CT or whole body PET-CT examinations
Key exclusion criteria (11 listed)
- dMMR or MSI-H patients
- Myelosuppression without obvious causes
- Locally advanced rectal cancer without high-risk factors
- Prior or concurrent other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix)
- Severe allergic reaction to other monoclonal antibodies
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 |
|---|---|---|
| Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy1. Radiotherapy: Radiotherapy location: primary site and the corresponding draining lymph node. Radiotherapy techniques: IMRT/VMRT. Radiotherapy dose and fractionation pattern: conventional external irradiation, 50Gy/25 fx/5 weeks or 25Gy/5fx/1 week. 2. Chemotherapy: Long-course radiotherapy concurrent with chemotherapy: capecitabine 825mg/m2, bid, d1-5/week. Short-course radiotherapy without concurrent chemotherapy. Consolidation chemotherapy and immunotherapy: QL1706 (iparomlimab and tuvonralimab 5mg/kg, d1) and CAPOX (Oxaliplatin 130mg/m2, d1 + capecitabine 1000mg/m2, bid, d1-14), repeated on a 21-day cycle, for 6 cycles. 3. Surgery or watch-and-wait Total mesorectal excision (TME), or watch-and-wait (for patients with clinical complete response). | Combination product | Dual immunotherapy group |
Primary outcome
Overall complete response (CR) rate
Time frame: 1 year
Overall complete response (CR) rate, meaning the rates of pathological complete response (pCR) plus clinical complete response (cCR).
6 secondary outcomes
Overall survival (OS)
Time frame: 3 year
Rate of surgical complications
Time frame: 1 year
Organ preservation rate
Time frame: 1 year
3 year disease free survival (DFS) rate
Time frame: 3 year
3 year local recurrence free survival (LRFS) rate
Time frame: 3 year
The incidence and grade of adverse events
Time frame: 1 year
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 13 Oct 2026.
- Derived from this study: PubMed 41654222Zhu Z, Zhang X, Yun Z, Wang C, Li W, Ma L, Xu L, Sun Y, Yu J, Yue J. [18F] AlF-NOTA-FAPI-04 PET/CT scans can predict pathologic complete response in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Radiother Oncol. 2026 Apr;217:111429. doi: 10.1016/j.radonc.2026.111429. Epub 2026 Feb 5.
- 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.
Jinbo Yue, Docter principal investigator
Shandong Cancer Hospital and Institute, Department of Radiation Oncology
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 Total neoadjuvant therapy integrating iparomlimab/tuvonralimab with chemoradiotherapy in people with Rectal Malignant Neoplasms, run by Shandong Cancer Hospital and Institute 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 11 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: looking for participants now, as of the sponsor's last update on 13 Oct 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 Jinbo Yue, Docter (0531-67626441, jbyue@sdfmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall complete response (CR) rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07026422, which also lists 1 linked publication.
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 13 Oct 2026.