Colorectal NeoplasmsPhase 2NCT07007728
Iparomlimab/Tuvonralimab Combined With Bevacizumab and CAPEOX as Conversion Therapy for Colorectal Cancer Liver Metastasis
A Phase 2 study testing Iparomlimab/Tuvonralimab, Bevacizumab + CAPEOX and Surgical resection ± ablation or stereotactic radiotherapy (if applicable) in people with Colorectal Neoplasms and Secondary Malignant Neoplasm of Liver, run by Peking University Cancer Hospital & Institute at 1 site in China.
Trial summary
More than half of colorectal cancer (CRC) patients present with RAS mutations or right-sided primary tumors; however, objective response rates (ORRs) to bevacizumab combined with chemotherapy remain suboptimal. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Colorectal Neoplasms, Secondary Malignant Neoplasm of Liver
- What is being tested?
- Iparomlimab/Tuvonralimab, Bevacizumab + CAPEOX and Surgical resection ± ablation or stereotactic radiotherapy (if applicable)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2025to 31 Dec 2026
- 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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who meet all the following criteria will be included in this study:
- Sign written informed consent before initiating any trial-related procedures;
- ≥18 years and ≤79 years old, regardless of gender;
- Pathologically confirmed colorectal adenocarcinoma with liver metastases confirmed by pathology or imaging;
- No prior first-line systemic therapy (e.g., targeted therapy, immunotherapy, systemic chemotherapy) for liver metastases;
- At least one radiographically measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1);
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- Multidisciplinary team (MDT)-confirmed initially unresectable liver metastases (criteria for unresectability: inability to achieve R0/R1 resection via surgery, or anticipated residual liver volume <30% post-resection, or inability to preserve adequate hepatic inflow/outflow for residual liver). Patients with extrahepatic metastases (excluding brain/bone metastases) amenable to local treatment are eligible;
- Genetic testing results confirming either RAS mutation or right-sided colon location with RAS wild-type status, absence of BRAF V600E mutation, and microsatellite stability (MSS)/proficient mismatch repair (pMMR) confirmed through immunohistochemistry (IHC) or PCR testing.
- ECOG performance status score 0-1;
- Life expectancy ≥12 weeks;
- No indications for emergency surgery due to primary tumor complications including significant bleeding or obstruction;
- Adequate organ function meeting the following laboratory parameters:
- Absolute neutrophil count (ANC) ≥1.5×10^9/L without granulocyte colony-stimulating factor support within 14 days; ii. Platelet count (PLT) ≥75×10^9/L without transfusion within 14 days; iii. Hemoglobin (HGB) >70 g/L without transfusion or erythropoietin use within 14 days; iv. Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); serum albumin (Alb) ≥28.0 g/L; v. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5×ULN; vi. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 mL/min; vii. Normal coagulation function: International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5×ULN;
- Fertile female patients or male patients with fertile partners must agree to use highly effective contraception (failure rate <1% per year) from 7 days before first dose until 24 weeks post-treatment;
- Fertile female patients must have negative serum pregnancy test within 7 days before first dose;
- Patients must be capable of and willing to comply with study protocol requirements, including scheduled visits, treatment plans, laboratory tests, and other trial-related procedures.
Who cannot join
- Patients who meet any of the following exclusion criteria will be excluded from this study:
- Patients intolerant to systemic chemotherapy or surgery;
- Liver metastases occurring during or within 6 months after oxaliplatin-based adjuvant chemotherapy for the primary tumor;
- Major surgery within 6 weeks before treatment initiation, anticipated requirement for major surgery during the study, or presence of severe traumatic injury, fractures, ulcers, or non-healing wounds;
- History of myocardial infarction, severe/unstable angina, coronary artery bypass grafting, or heart failure (NYHA class III-IV) within 3 months before treatment initiation;
- Prior treatment with immune checkpoint inhibitors (e.g., anti-PD-1/L1, CTLA-4 inhibitors);
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- Concurrent or prior malignancies;
- History of autoimmune diseases or allogeneic stem cell/solid organ transplant (excluding corneal transplant) rendering immunotherapy intolerance;
- Moderate-to-severe allergic reactions, hypersensitivity, or intolerance to antibody-based therapies;
- Clinically significant bleeding symptoms or high bleeding risk within 3 months before treatment initiation (e.g., gastrointestinal bleeding, gastroesophageal varices, hemorrhagic gastric ulcer, or history of hematochezia, hematemesis, or hemoptysis);
- Clinically symptomatic ascites/pleural/pericardial effusion requiring therapeutic intervention;
- Primary tumor obstruction, perforation or intra-abdominal infection within 3 months before treatment initiation, without appropriate management;
- Known hypersensitivity to active pharmaceutical ingredient or excipients of the investigational drug;
- Dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, gastrointestinal perforation, malabsorption syndrome, or uncontrolled inflammatory bowel disease;
- Pregnant or breastfeeding women;
- Concurrent participation in other clinical trials;
- Any other condition deemed inappropriate for study participation by the investigator.
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
Peking University Cancer Hospital & Institute
Beijing, Beijing Municipality, 100142
Kun Wang, +86 13910726401, wang-kun@vip.sina.com
About this study
Official title: Efficacy and Safety of Iparomlimab/Tuvonralimab Combined With Bevacizumab and CAPEOX as Conversion Therapy in Patients With Right-Sided or RAS-mutant, Microsatellite Stable, Initially Unresectable Colorectal Cancer Liver Metastasis: A Prospective, Open-Label, Single-Arm, Single-Center, Phase II Clinical Trial
More than half of colorectal cancer (CRC) patients present with RAS mutations or right-sided primary tumors; however, objective response rates (ORRs) to bevacizumab combined with chemotherapy remain suboptimal. Additionally, approximately 95% of metastatic CRC (mCRC) cases are microsatellite stable (MSS), where immune checkpoint inhibitor monotherapy demonstrates limited efficacy, necessitating combination strategies. Iparomlimab/tuvonralimab is the first bifunctional combination of anti-PD-1/anti-CTLA-4 monoclonal antibodies, which has shown therapeutic promise in first-line mCRC when combined with bevacizumab and capecitabine plus oxaliplatin (CAPEOX). Nevertheless, whether improved treatment response rates in mCRC patients can lead to higher surgical conversion rates remains unclear. This study evaluates the efficacy and safety of iparomlimab/tuvonralimab combined with bevacizumab and CAPEOX as conversion therapy in patients with right-sided or RAS-mutant, MSS, initially unresectable colorectal cancer liver metastasis.
- Being tested
- Iparomlimab/Tuvonralimab, Bevacizumab + CAPEOX, Surgical resection ± ablation or stereotactic radiotherapy (if applicable)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iparomlimab/TuvonralimabDrug
5mg/kg intravenous infusion on Day 1 of each cycle (every 21 days). Duration: 3 or 6 cycles
Bevacizumab + CAPEOXDrug
Bevacizumab: 7.5mg/kg intravenous infusion on Day 1 of each cycle (every 21 days).
Capecitabine: 1000 mg/m2 twice daily orally on Day 1-14 of each cycle (every 21 days).
Oxaliplatin: 130 mg/m2 intravenous infusion on Day 1 of each cycle (every 21 days).
Duration:
Conversion therapy phase: 3 or 6 cycles; Postoperative follow-up phase (for patients with successful conversion surgery ): 3 or 6 cycles (a total perioperative duration of 9 cycles); Maintenance phase (for patients without successful conversion surgery ): Continuous therapy until disease progression, intolerable adverse events, withdrawal of consent, loss to follow-up, death, or study termination.
Surgical resection ± ablation or stereotactic radiotherapy (if applicable)Procedure or surgery
After 3 or 6 cycles of conversion therapy, surgical resection ± ablation or stereotactic radiotherapy will be provided if applicable.
| Study group | Role | What they receive |
|---|---|---|
| Iparomlimab/Tuvonralimab Combined with Bevacizumab and CAPEOX | Experimental | Not described Receives: Drug: Iparomlimab/Tuvonralimab; Drug: Bevacizumab + CAPEOX; Procedure: Surgical resection ± ablation or stereotactic radiotherapy (if applicable) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
The proportion of subjects achieving complete response or partial response, assessed by investigators according to RECIST 1.1 criteria.
Measured: Following 3 or 6 cycles (each cycle is ~21 days) of the treatment, approximately 9 or 18 weeks overall
Secondary outcomes (4)
Surgical Conversion Rate
The proportion of subjects with successful conversion surgery. The criteria for successful conversion are as follows: evaluation of liver metastases achieves partial response after the conversion therapy; liver tumor-free status can be achieved through surgical resection ± ablation or stereotactic radiotherapy, with a residual liver volume exceeding 40%; liver function is classified as Child-Pugh Class A, and other liver function and laboratory parameters meet surgical and anesthesia requirements.
Measured: Following 3 or 6 cycles (each cycle is ~21 days) of the treatment, approximately 9 or 18 weeks overall
Major Pathological Response Rate
The proportion of subjects in whom postoperative pathological evaluation of liver metastases shows either no residual tumor cells (complete regression) or residual tumor cells comprising 1-49% of the specimen.
Measured: Perioperative/Periprocedural
Progression-free Survival
The time from the initiation of treatment until disease progression or death from any cause, whichever occurs first.
Measured: From the date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Overall Survival
The time from the initiation of treatment until death from any cause.
Measured: From the date of treatment initiation until the date of death from any cause, assessed up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2025
- Study start1 Jun 2025 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Peking University Cancer Hospital & InstituteThe 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
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wang Kun, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07007728
- Sponsor's protocol ID
- DUALTRANSFORM (PKUCRLM-02)
- Status last verified
- Jun 2025
- First submitted
- 15 May 2025
- Last updated
- 6 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The investigator has no individual patient data (IPD) sharing plan.
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Iparomlimab/Tuvonralimab Combined With Bevacizumab and CAPEOX as Conversion Therapy in Patients With Right-Sided or RAS-mutant, Microsatellite Stable, Initially Unresectable Colorectal Cancer Liver Metastasis: A Prospective, Open-Label, Single-Arm, Single-Center, Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT07007728
- Acronym / sponsor ID
- DUALTRANSFORM (PKUCRLM-02)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Study start
- 1 Jun 2025 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 6 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.
More than half of colorectal cancer (CRC) patients present with RAS mutations or right-sided primary tumors; however, objective response rates (ORRs) to bevacizumab combined with chemotherapy remain suboptimal. Additionally, approximately 95% of metastatic CRC (mCRC) cases are microsatellite stable (MSS), where immune checkpoint inhibitor monotherapy demonstrates limited efficacy, necessitating combination strategies. Iparomlimab/tuvonralimab is the first bifunctional combination of anti-PD-1/anti-CTLA-4 monoclonal antibodies, which has shown therapeutic promise in first-line mCRC when combined with bevacizumab and capecitabine plus oxaliplatin (CAPEOX). Nevertheless, whether improved treatment response rates in mCRC patients can lead to higher surgical conversion rates remains unclear. This study evaluates the efficacy and safety of iparomlimab/tuvonralimab combined with bevacizumab and CAPEOX as conversion therapy in patients with right-sided or RAS-mutant, MSS, initially unresectable colorectal cancer liver metastasis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Iparomlimab/Tuvonralimab Combined with Bevacizumab and CAPEOX | Experimental | Drug: Iparomlimab/Tuvonralimab, Drug: Bevacizumab + CAPEOX, Procedure: Surgical resection ± ablation or stereotactic radiotherapy (if applicable) |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Sign written informed consent before initiating any trial-related procedures;
- ≥18 years and ≤79 years old, regardless of gender;
- Pathologically confirmed colorectal adenocarcinoma with liver metastases confirmed by pathology or imaging;
- No prior first-line systemic therapy (e.g., targeted therapy, immunotherapy, systemic chemotherapy) for liver metastases;
- At least one radiographically measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1);
Key exclusion criteria (17 listed)
- Patients who meet any of the following exclusion criteria will be excluded from this study:
- Patients intolerant to systemic chemotherapy or surgery;
- Liver metastases occurring during or within 6 months after oxaliplatin-based adjuvant chemotherapy for the primary tumor;
- Major surgery within 6 weeks before treatment initiation, anticipated requirement for major surgery during the study, or presence of severe traumatic injury, fractures, ulcers, or non-healing wounds;
- History of myocardial infarction, severe/unstable angina, coronary artery bypass grafting, or heart failure (NYHA class III-IV) within 3 months before treatment initiation;
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 |
|---|---|---|
| Iparomlimab/Tuvonralimab5mg/kg intravenous infusion on Day 1 of each cycle (every 21 days). Duration: 3 or 6 cycles | Drug | Iparomlimab/Tuvonralimab Combined with Bevacizumab and CAPEOX |
| Bevacizumab + CAPEOXBevacizumab: 7.5mg/kg intravenous infusion on Day 1 of each cycle (every 21 days). Capecitabine: 1000 mg/m2 twice daily orally on Day 1-14 of each cycle (every 21 days). Oxaliplatin: 130 mg/m2 intravenous infusion on Day 1 of each cycle (every 21 days). Duration: Conversion therapy phase: 3 or 6 cycles; Postoperative follow-up phase (for patients with successful conversion surgery ): 3 or 6 cycles (a total perioperative duration of 9 cycles); Maintenance phase (for patients without successful conversion surgery ): Continuous therapy until disease progression, intolerable adverse events, withdrawal of consent, loss to follow-up, death, or study termination. | Drug | Iparomlimab/Tuvonralimab Combined with Bevacizumab and CAPEOX |
| Surgical resection ± ablation or stereotactic radiotherapy (if applicable)After 3 or 6 cycles of conversion therapy, surgical resection ± ablation or stereotactic radiotherapy will be provided if applicable. | Procedure or surgery | Iparomlimab/Tuvonralimab Combined with Bevacizumab and CAPEOX |
Primary outcome
Objective Response Rate
Time frame: Following 3 or 6 cycles (each cycle is ~21 days) of the treatment, approximately 9 or 18 weeks overall
The proportion of subjects achieving complete response or partial response, assessed by investigators according to RECIST 1.1 criteria.
4 secondary outcomes
Surgical Conversion Rate
Time frame: Following 3 or 6 cycles (each cycle is ~21 days) of the treatment, approximately 9 or 18 weeks overall
Major Pathological Response Rate
Time frame: Perioperative/Periprocedural
Progression-free Survival
Time frame: From the date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Overall Survival
Time frame: From the date of treatment initiation until the date of death from any cause, assessed up to 18 months
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 6 Jun 2025.
- Individual participant dataSharing planned: No. The investigator has no individual patient data (IPD) sharing plan.
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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 Iparomlimab/Tuvonralimab, Bevacizumab + CAPEOX and Surgical resection ± ablation or stereotactic radiotherapy (if applicable) in people with Colorectal Neoplasms and Secondary Malignant Neoplasm of Liver, run by Peking University Cancer Hospital & 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 16 inclusion and 17 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 6 Jun 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?
Contact Kun Wang (+86 13910726401, wang-kun@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Following 3 or 6 cycles (each cycle is ~21 days) of the treatment, approximately 9 or 18 weeks overall). 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 6 Jun 2025.