Colorectal CancerPhase 2/3NCT06280495
Neoadjuvant Serplulimab & Bevacizumab With FOLFOX vs. FOLFOX Alone in RAS/BRAF WT, pMMR/MSS CRC Patients
A Phase 2/3 study testing Oxaliplatin, Fluorouracil and Serplulimab in people with Colorectal Cancer and Liver Metastases, run by Sun Yat-sen University at 1 site in China.
Trial summary
The primary objective of this study is to assess whether the addition of Serplulimab (a PD-1 inhibitor) and Bevacizumab (an anti-angiogenesis agent) to the standard FOLFOX chemotherapy can enhance the immune microenvironment in the liver, increase T lymphocyte infiltration, and consequently improve the postoperative… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer, Liver Metastases
- What is being tested?
- Oxaliplatin, Fluorouracil and Serplulimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2024to 31 Dec 2029
- Phase
- Phase 2/3
- 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 and ≤75 years old
- Histologically confirmed colorectal adenocarcinoma
- Radiological and/or pathological confirmation of liver metastases, with ≤5 lesions
- Genetic testing and/or immunohistochemistry confirmation of RAS, BRAF wild-type, and pMMR/MSS
- Absence of extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary)
- Primary colorectal tumor has been or can be radically resected
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- Liver metastatic lesions are resectable (including radiofrequency ablation and SBRT), and postoperative NED (no evidence of disease) is expected. Resectable liver metastases are specifically defined as ① ≤5 metastatic lesions; ② R0 resection can be performed (including radiofrequency ablation and SBRT); ③ Sufficient residual liver volume is expected after resection; ④ At least one hepatic vein can be preserved after resection, with preserved blood flow in and out of the residual liver and preserved bile ducts, and can preserve at least two adjacent liver segments; ⑤ No extrahepatic metastases.
- No prior anti-tumor therapy for liver metastases, except for surgical resection of primary lesions
- Normal hematological function (platelets >90×109/L; white blood cells >3×109/L; neutrophils >1.5×109/L)
- Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminases ≤5 times ULN, alkaline phosphatase ≤2.5 ULN, no ascites, normal coagulation function, albumin ≥35g/L
- Liver function classified as Child-Pugh grade A
- Serum creatinine below the upper limit of normal (ULN), or calculated creatinine clearance rate >50ml/min (using Cockcroft-Gault formula)
- ECOG performance status 0-1
- Expected lifespan >3 months
- Signed written informed consent
- Willing and able to be followed up until death or end of study or study termination.
Who cannot join
- Diagnosis of colorectal cancer with distant extrahepatic metastases
- Prior chemotherapy, targeted therapy, intervention, or immunotherapy for liver metastases
- No planned surgical resection for liver metastatic lesions
- Received oxaliplatin-containing adjuvant chemotherapy regimen within the past one year
- Any toxicity residuals from previous chemotherapy, excluding alopecia, such as peripheral neuropathy ≥NCI CTC v3.0 grade 2
- Use of immunosuppressive drugs one week prior to study treatment initiation, excluding topical corticosteroids via nasal, inhalational, or other routes or physiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/day of prednisone or equivalent) or steroids used for prevention of contrast agent allergy
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- Interstitial lung disease requiring corticosteroid treatment
- Known active autoimmune disease requiring symptomatic treatment or with a history of such disease within the past 2 years. Patients with vitiligo, psoriasis, alopecia, or Graves' disease who have not required systemic treatment within the past 2 years, patients with hypothyroidism requiring only thyroid hormone replacement therapy, and patients with type I diabetes requiring only insulin replacement therapy can be included
- Known history of primary immunodeficiency
- Patients with active tuberculosis
- History of allogeneic organ or hematopoietic stem cell transplantation
- Known allergy to any monoclonal antibody or chemotherapy drug (Fluorouracil, oxaliplatin) preparation or excipient component
- Bleeding tendency or coagulation disorder
- Significant symptoms of intestinal obstruction
- Hypertensive crisis or hypertensive encephalopathy
- Severe uncontrolled systemic complications such as infection or diabetes
- Clinically severe cardiovascular diseases such as cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), hypertension that remains uncontrolled after appropriate drug treatment, unstable angina pectoris, congestive heart failure (NYHA 2-4), or arrhythmia requiring medication
- Past or physical examination showing central nervous system diseases (such as primary brain tumor, epilepsy uncontrolled by standard treatment, any history of brain metastasis, or stroke)
- Diagnosis of other malignant tumors within the past 5 years (excluding basal cell carcinoma and/or carcinoma in situ of the cervix after radical surgery)
- Patients who received any investigational drug therapy within the last 28 days prior to the study
- Pregnant or lactating women and women of childbearing age not using or refusing to use effective non-hormonal contraception (intrauterine devices, barrier contraception combined with spermicidal gel, or sterilization surgery) or men with reproductive potential unwilling or unable to comply with the study protocol
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
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Yu-hong Li, MD, Ph D, liyh@sysucc.org.cn
Yu-hong Li, MD, Ph D
About this study
Official title: Neoadjuvant Combination of Serplulimab and Bevacizumab With FOLFOX Versus FOLFOX Alone for Resectable Liver Metastases in RAS/BRAF Wild-Type, pMMR/MSS Colorectal Cancer Patients
The primary objective of this study is to assess whether the addition of Serplulimab (a PD-1 inhibitor) and Bevacizumab (an anti-angiogenesis agent) to the standard FOLFOX chemotherapy can enhance the immune microenvironment in the liver, increase T lymphocyte infiltration, and consequently improve the postoperative prognosis for patients with surgically resectable colorectal cancer liver metastases (RAS/BRAF wild-type, pMMR/MSS) compared to FOLFOX alone.
Read the detailed description
In this prospective, multi-center clinical trial titled "INTENSIFY," we seek to evaluate the potential benefits of integrating Serplulimab and Bevacizumab with the standard FOLFOX chemotherapy regimen as neoadjuvant treatment for surgically resectable colorectal cancer liver metastases (CRLM). Colorectal cancer remains a leading cause of global cancer-related morbidity and mortality, with liver metastases accounting for a significant proportion. Our primary objective is to investigate whether the addition of Serplulimab, a PD-1 inhibitor, and Bevacizumab, an anti-angiogenesis agent, can improve the postoperative prognosis for patients with RAS/BRAF wild-type, pMMR/MSS CRLM. We aim to address critical questions regarding the efficacy of this combined treatment in enhancing the immune microenvironment within the liver, ultimately leading to increased T lymphocyte infiltration and improved patient outcomes. The study will involve a randomized assignment of patients to either the standard FOLFOX chemotherapy arm or the experimental arm receiving FOLFOX in combination with Serplulimab and Bevacizumab. Participants will undergo neoadjuvant treatment, surgical resection, and regular follow-up assessments to evaluate treatment response, recurrence rates, and overall survival. By comparing outcomes between the two groups, specifically assessing factors like recurrence-free survival, overall survival, and changes in the immune microenvironment, we aim to provide valuable insights into the optimization of treatment strategies for this specific subset of colorectal cancer patients.
- Conditions
- Colorectal Cancer, Liver Metastases
- Being tested
- Oxaliplatin, Fluorouracil, Serplulimab, Bevacizumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
Also called Eloxatin
5 mg/m2 IV on day 1
FluorouracilDrug
Also called 5-FU
400 mg/m2 IV bolus on day 1, followed by 2.4 g/m2 continuous IV infusion over 48 hours
SerplulimabDrug
Also called anti-PD-1 antibody
200 mg IV infusion on day 1
BevacizumabDrug
Also called Avastin
5 mg/kg IV infusion on day 1
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX only group | Active comparator | Oxaliplatin: 85 mg/m2 IV on day 1 Fluorouracil (FU): 400 mg/m2 IV bolus on day 1, followed by 2.4 g/m2 continuous IV infusion over 48 hours Leucovorin: 200 mg/m2 IV on day 1 This treatment regimen is repeated every two weeks for a total of 6 cycles. Receives: Drug: Oxaliplatin; Drug: Fluorouracil |
| Serplulimab + Bevacizumab + FOLFOX | Experimental | Serplulimab: 200 mg IV infusion on day 1 Bevacizumab: 5 mg/kg IV infusion on day 1 Oxaliplatin, FU, and Leucovorin as per the control arm The experimental arm follows the same treatment schedule as the standard FOLFOX regimen, with the addition of Serplulimab and Bevacizumab for the first 3 cycles only. Receives: Drug: Oxaliplatin; Drug: Fluorouracil; Drug: Serplulimab; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year Progression-Free Survival Rate
The proportion of patients who, following the initiation of treatment, remain both alive and without evidence of disease progression for a consecutive period of three years.
Measured: Assessed for three years following the initiation of treatment
Secondary outcomes (6)
Median Overall Survival
The duration of time from diagnosis until death
Measured: Assessed throughout the study duration (5 years)
Major Pathological Response (MPR)
Defined as residual viable tumor of less than or equal to 10%
Measured: Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)
Pathologic complete response (pCR)
The absence of tumor cells in all specimens.
Measured: Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)
Pathological Partial Response
Defined as residual viable tumor of more than 10% but less than 50%
Measured: Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)
Disease Free Survival
The measure of time after treatment during which no sign of cancer is found
Measured: Assessed throughout the study duration (5 years)
Treatment-related adverse events
Assessment of adverse events related to the treatment received in both arms
Measured: Assessed throughout the study duration (5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start1 Feb 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, randomized, multicenter clinical trial. Stratified randomization based on liver metastasis characteristics, including timing, number, and size, will be conducted in eligible patients.
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yuhong Li, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06280495
- Sponsor's protocol ID
- INTENSIFY-CRC
- Status last verified
- Apr 2026
- First submitted
- 20 Feb 2024
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data and materials used in this study can be made available following study completion upon reasonable request to the corresponding author, subject to ethical and legal considerations and applicable data-sharing agreements.
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Combination of Serplulimab and Bevacizumab With FOLFOX Versus FOLFOX Alone for Resectable Liver Metastases in RAS/BRAF Wild-Type, pMMR/MSS Colorectal Cancer Patients
- ClinicalTrials.gov ID
- NCT06280495
- Acronym / sponsor ID
- INTENSIFY-CRC
- Conditions
- Colorectal Cancer, Liver Metastases
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 156 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Feb 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 28 Feb 2024 (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.
The primary objective of this study is to assess whether the addition of Serplulimab (a PD-1 inhibitor) and Bevacizumab (an anti-angiogenesis agent) to the standard FOLFOX chemotherapy can enhance the immune microenvironment in the liver, increase T lymphocyte infiltration, and consequently improve the postoperative prognosis for patients with surgically resectable colorectal cancer liver metastases (RAS/BRAF wild-type, pMMR/MSS) compared to FOLFOX alone.
Detailed description
In this prospective, multi-center clinical trial titled "INTENSIFY," we seek to evaluate the potential benefits of integrating Serplulimab and Bevacizumab with the standard FOLFOX chemotherapy regimen as neoadjuvant treatment for surgically resectable colorectal cancer liver metastases (CRLM). Colorectal cancer remains a leading cause of global cancer-related morbidity and mortality, with liver metastases accounting for a significant proportion. Our primary objective is to investigate whether the addition of Serplulimab, a PD-1 inhibitor, and Bevacizumab, an anti-angiogenesis agent, can improve the postoperative prognosis for patients with RAS/BRAF wild-type, pMMR/MSS CRLM. We aim to address critical questions regarding the efficacy of this combined treatment in enhancing the immune microenvironment within the liver, ultimately leading to increased T lymphocyte infiltration and improved patient outcomes. The study will involve a randomized assignment of patients to either the standard FOLFOX chemotherapy arm or the experimental arm receiving FOLFOX in combination with Serplulimab and Bevacizumab. Participants will undergo neoadjuvant treatment, surgical resection, and regular follow-up assessments to evaluate treatment response, recurrence rates, and overall survival. By comparing outcomes between the two groups, specifically assessing factors like recurrence-free survival, overall survival, and changes in the immune microenvironment, we aim to provide valuable insights into the optimization of treatment strategies for this specific subset of colorectal cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective, randomized, multicenter clinical trial. Stratified randomization based on liver metastasis characteristics, including timing, number, and size, will be conducted in eligible patients.
| Arm | Type | Receives |
|---|---|---|
| FOLFOX only group | Active comparator | Drug: Oxaliplatin, Drug: FluorouracilOxaliplatin: 85 mg/m2 IV on day 1 Fluorouracil (FU): 400 mg/m2 IV bolus on day 1, followed by 2.4 g/m2 continuous IV infusion over 48 hours Leucovorin: 200 mg/m2 IV on day 1 This treatment regimen is repeated every two weeks for a total of 6 cycles. |
| Serplulimab + Bevacizumab + FOLFOX | Experimental | Drug: Oxaliplatin, Drug: Fluorouracil, Drug: Serplulimab, Drug: BevacizumabSerplulimab: 200 mg IV infusion on day 1 Bevacizumab: 5 mg/kg IV infusion on day 1 Oxaliplatin, FU, and Leucovorin as per the control arm The experimental arm follows the same treatment schedule as the standard FOLFOX regimen, with the addition of Serplulimab and Bevacizumab for the first 3 cycles only. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age ≥18 and ≤75 years old
- Histologically confirmed colorectal adenocarcinoma
- Radiological and/or pathological confirmation of liver metastases, with ≤5 lesions
- Genetic testing and/or immunohistochemistry confirmation of RAS, BRAF wild-type, and pMMR/MSS
- Absence of extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary)
Key exclusion criteria (21 listed)
- Diagnosis of colorectal cancer with distant extrahepatic metastases
- Prior chemotherapy, targeted therapy, intervention, or immunotherapy for liver metastases
- No planned surgical resection for liver metastatic lesions
- Received oxaliplatin-containing adjuvant chemotherapy regimen within the past one year
- Any toxicity residuals from previous chemotherapy, excluding alopecia, such as peripheral neuropathy ≥NCI CTC v3.0 grade 2
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 |
|---|---|---|
| OxaliplatinAlso: Eloxatin5 mg/m2 IV on day 1 | Drug | FOLFOX only group, Serplulimab + Bevacizumab + FOLFOX |
| FluorouracilAlso: 5-FU400 mg/m2 IV bolus on day 1, followed by 2.4 g/m2 continuous IV infusion over 48 hours | Drug | FOLFOX only group, Serplulimab + Bevacizumab + FOLFOX |
| SerplulimabAlso: anti-PD-1 antibody200 mg IV infusion on day 1 | Drug | Serplulimab + Bevacizumab + FOLFOX |
| BevacizumabAlso: Avastin5 mg/kg IV infusion on day 1 | Drug | Serplulimab + Bevacizumab + FOLFOX |
Primary outcome
3-year Progression-Free Survival Rate
Time frame: Assessed for three years following the initiation of treatment
The proportion of patients who, following the initiation of treatment, remain both alive and without evidence of disease progression for a consecutive period of three years.
6 secondary outcomes
Median Overall Survival
Time frame: Assessed throughout the study duration (5 years)
Major Pathological Response (MPR)
Time frame: Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)
Pathologic complete response (pCR)
Time frame: Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)
Pathological Partial Response
Time frame: Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)
Disease Free Survival
Time frame: Assessed throughout the study duration (5 years)
Treatment-related adverse events
Time frame: Assessed throughout the study duration (5 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 20 Apr 2026.
- Individual participant dataSharing planned: Undecided. Data and materials used in this study can be made available following study completion upon reasonable request to the corresponding author, subject to ethical and legal considerations and applicable data-sharing agreements.
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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 2/3 study testing Oxaliplatin, Fluorouracil and Serplulimab in people with Colorectal Cancer and Liver Metastases, run by Sun Yat-sen 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 16 inclusion and 21 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 20 Apr 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Yuhong Li, PhD (87342487 ext. 020, liyh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year Progression-Free Survival Rate (time frame: Assessed for three years following the initiation of treatment). 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 20 Apr 2026.