Colorectal CancerPhase 2NCT07604909
A Phase II Randomized Trial of Serplulimab With Second-Line Chemo/Targeted Therapy for Early Relapse Colorectal Cancer After Adjuvant Chemotherapy
A Phase 2 study testing Serplulimab and Second-Line Chemo/Targeted Therapy in people with Colorectal Cancer and Relapse, run by Fudan University at 1 site in China.
Trial summary
Approximately 20-50% of patients with colorectal cancer (CRC) develop distant metastasis after curative surgery, and those with early relapse within one year of completing adjuvant chemotherapy (XELOX or FOLFOX) have a particularly poor prognosis and limited treatment options. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Relapse
- What is being tested?
- Serplulimab and Second-Line Chemo/Targeted Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 10 May 2026to 10 Sep 2029
- 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
- Age ≥18 years, male or female. Histologically confirmed early relapse (within 1 year after surgery, UICC stage IV) of colorectal cancer after adjuvant chemotherapy, with initially unresectable metastatic lesions or refusal of surgery.
- Have received standard postoperative adjuvant chemotherapy (XELOX or FOLFOX). Before enrollment, tumor tissue tested by immunohistochemistry as pMMR, or by PCR or NGS as MSS or MSI-L.
- At least one measurable tumor lesion according to RECIST 1.1 criteria. ECOG performance status 0-1. Life expectancy ≥3 months.
- Adequate organ function:
- Neutrophils ≥1.5 × 10⁹/L; platelets ≥100 × 10⁹/L; hemoglobin ≥9 g/dL; serum albumin ≥3 g/dL.
- Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN), with T3 and T4 within normal range.
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- Bilirubin ≤1.5 × ULN; ALT and AST ≤2 × ULN.
- Serum creatinine ≤1.5 × ULN, creatinine clearance ≥60 mL/min.
- International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN, unless the patient is receiving anticoagulant therapy and PT is within the expected therapeutic range for anticoagulation.
- Activated partial thromboplastin time (aPTT) ≤1.5 × ULN. Female patients of childbearing potential must have a negative pregnancy test. Female patients not of childbearing potential, fertile male patients, and female patients of childbearing potential at risk of pregnancy must agree to use adequate contraception throughout the study and for 12 months after the last dose of study treatment.
- Signed and dated written informed consent indicating that the patient has been informed of all relevant aspects of the study.
- Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Pathologically diagnosed other intestinal tumors, such as gastrointestinal stromal tumors.
- RAS mutation status not tested. Tumor tissue tested by immunohistochemistry as dMMR, or by PCR or NGS as MSI-H. Metastatic lesions are resectable, or the patient wishes to undergo metastasectomy.
- Uncontrolled active bleeding from the primary tumor or intestinal obstruction. Contraindications to immune checkpoint inhibitor therapy. Hypersensitivity to study drugs or their excipients. Prior or concurrent other malignancy, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma.
- Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); excluding autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone, type I diabetes mellitus treated with stable doses of insulin, vitiligo, or childhood asthma/allergy that has resolved and requires no intervention in adulthood.
- History of immunodeficiency, including HIV positivity, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation.
- History of interstitial lung disease or non-infectious pneumonitis. Active pulmonary tuberculosis infection by history or CT scan, or history of active pulmonary tuberculosis infection within 1 year before enrollment, or history of active pulmonary tuberculosis infection more than 1 year prior without adequate treatment.
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- Active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL) or hepatitis C (positive HCV antibody with HCV-RNA above the lower limit of detection of the assay).
- Severe cardiac, pulmonary, renal, or hepatic dysfunction. Hypertension that cannot be adequately controlled with antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
- History of psychotropic substance abuse, alcoholism, or drug addiction. Other factors that may affect patient safety or trial compliance as judged by the investigator, such as serious diseases requiring concomitant treatment (including psychiatric disorders), serious laboratory abnormalities, or other family or social factors.
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
Fudan University Shanghai Cancer Center
Shanghai
Qingguo Li, M.D., 18918298120, qingguoli@fudan.edu.cn
About this study
Official title: A Phase II, Prospective, Randomized Study of Serplulimab Plus Second-Line Chemotherapy and Targeted Therapy vs Second-Line Chemotherapy and Targeted Therapy Alone in Patients With Early Relapse of Colorectal Cancer After Adjuvant Chemotherapy
Approximately 20-50% of patients with colorectal cancer (CRC) develop distant metastasis after curative surgery, and those with early relapse within one year of completing adjuvant chemotherapy (XELOX or FOLFOX) have a particularly poor prognosis and limited treatment options. Standard second-line therapy with FOLFIRI plus targeted therapy (bevacizumab or cetuximab) often yields suboptimal outcomes in this population. Moreover, over 95% of these patients have pMMR/MSS tumors, which are inherently resistant to immune checkpoint inhibitor monotherapy.
This phase II, prospective, randomized trial aims to evaluate the efficacy and safety of adding serplulimab, a PD-1 inhibitor, to second-line chemotherapy plus targeted therapy in patients with early-relapse CRC after adjuvant chemotherapy. Eligible patients with pMMR/MSS or MSI-L tumors will be randomly assigned (1:1) to either the experimental arm (serplulimab plus FOLFIRI and targeted therapy) or the control arm (FOLFIRI plus targeted therapy alone). Randomization is stratified by primary tumor location (left vs. right colon), initial disease status (liver-only vs. extrahepatic metastasis), and RAS status (wild-type vs. mutant). A total of 40 patients (20 per arm) will be enrolled using a Pick-the-Winner design.
Read more
The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), overall survival (OS), R0 resection rate, and safety (NCI-CTCAE v5.0). Exploratory biomarker analyses in tumor tissue and blood (e.g., PD-L1 expression, tumor mutational burden, lymphocyte subsets, cytokines, TCR sequencing, circulating tumor DNA, and gut microbiome) will be performed to identify potential predictors of response and resistance.
This is the first prospective randomized study specifically targeting early-relapse CRC after adjuvant chemotherapy. The findings will provide high-level evidence on whether adding PD-1 blockade to standard chemo-targeted therapy can improve outcomes in this high-risk, understudied population and may inform future phase III trials.
- Conditions
- Colorectal Cancer, Relapse
- Being tested
- Serplulimab, Second-Line Chemo/Targeted Therapy
- Medical subject headings
- Colorectal Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SerplulimabDrug
Serplulimab: 3 mg/kg intravenously on Day 1, repeated every 2 weeks
Second-Line Chemo/Targeted TherapyDrug
Left-sided, RAS wild-type
Treatment Regimen:
Cetuximab 400 mg/m², intravenous infusion, first infusion over >2 hours, then 250 mg/m² intravenous infusion over ≥60 minutes, repeated weekly;
FOLFIRI:
Irinotecan 180 mg/m², intravenous infusion over 90 minutes, Day 1; Leucovorin (LV) 400 mg/m², intravenous infusion over 2 hours, Day 1; 5-FU 400 mg/m², intravenous bolus, Day 1; followed by 2400 mg/m² infusion over 46-48 hours; Repeated every 2 weeks
Right-sided, RAS mutant
Treatment Regimen:
Bevacizumab 5 mg/kg, intravenous infusion, Day 1, repeated every 2 weeks
FOLFIRI:
Irinotecan 180 mg/m², intravenous infusion over 90 minutes, Day 1; Leucovorin (LV) 400 mg/m², intravenous infusion over 2 hours, Day 1; 5-FU 400 mg/m², intravenous bolus, Day 1; followed by 2400 mg/m² infusion over 46-48 hours; Repeated every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | Not described Receives: Drug: Serplulimab; Drug: Second-Line Chemo/Targeted Therapy |
| Control Group | Active comparator | Not described Receives: Drug: Second-Line Chemo/Targeted Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
Progression-free survival (PFS) is defined as the time from randomization to the first documented tumor progression or death from any cause.
Measured: 12 months
Secondary outcomes (4)
Objective response rate (ORR = CR + PR)
Objective response rate (ORR = CR + PR): The proportion of patients whose best overall response is complete response or partial response.
Measured: 12 months
Disease control rate (DCR = CR + PR + SD)
Disease control rate (DCR = CR + PR + SD): The proportion of patients whose best overall response is complete response, partial response, or stable disease.
Measured: 12 months
R0 resection rate
R0 resection rate: The proportion of tumors in which pathological examination confirms no residual cancer cells at the surgical margin (resection margin) after surgery.
Measured: 12 months
Overall survival (OS)
Overall survival (OS): The time from randomization to death from any cause.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2026
- Study start10 May 2026
- Primary completion10 Sep 2027 (estimated)
- Study completion10 Sep 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 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
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Qingguo Li, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07604909
- Sponsor's protocol ID
- EARLY-REACT Trial
- Status last verified
- May 2026
- First submitted
- 17 May 2026
- Last updated
- 22 May 2026
- Results posted
- 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 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Prospective, Randomized Study of Serplulimab Plus Second-Line Chemotherapy and Targeted Therapy vs Second-Line Chemotherapy and Targeted Therapy Alone in Patients With Early Relapse of Colorectal Cancer After Adjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT07604909
- Acronym / sponsor ID
- EARLY-REACT Trial
- Conditions
- Colorectal Cancer, Relapse
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 10 May 2026 (actual)
- Primary completion
- 10 Sep 2027 (estimated)
- Study completion
- 10 Sep 2029 (estimated)
- First posted
- 22 May 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.
Approximately 20-50% of patients with colorectal cancer (CRC) develop distant metastasis after curative surgery, and those with early relapse within one year of completing adjuvant chemotherapy (XELOX or FOLFOX) have a particularly poor prognosis and limited treatment options. Standard second-line therapy with FOLFIRI plus targeted therapy (bevacizumab or cetuximab) often yields suboptimal outcomes in this population. Moreover, over 95% of these patients have pMMR/MSS tumors, which are inherently resistant to immune checkpoint inhibitor monotherapy.
This phase II, prospective, randomized trial aims to evaluate the efficacy and safety of adding serplulimab, a PD-1 inhibitor, to second-line chemotherapy plus targeted therapy in patients with early-relapse CRC after adjuvant chemotherapy. Eligible patients with pMMR/MSS or MSI-L tumors will be randomly assigned (1:1) to either the experimental arm (serplulimab plus FOLFIRI and targeted therapy) or the control arm (FOLFIRI plus targeted therapy alone). Randomization is stratified by primary tumor location (left vs. right colon), initial disease status (liver-only vs. extrahepatic metastasis), and RAS status (wild-type vs. mutant). A total of 40 patients (20 per arm) will be enrolled using a Pick-the-Winner design.
The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), overall survival (OS), R0 resection rate, and safety (NCI-CTCAE v5.0). Exploratory biomarker analyses in tumor tissue and blood (e.g., PD-L1 expression, tumor mutational burden, lymphocyte subsets, cytokines, TCR sequencing, circulating tumor DNA, and gut microbiome) will be performed to identify potential predictors of response and resistance.
This is the first prospective randomized study specifically targeting early-relapse CRC after adjuvant chemotherapy. The findings will provide high-level evidence on whether adding PD-1 blockade to standard chemo-targeted therapy can improve outcomes in this high-risk, understudied population and may inform future phase III trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Drug: Serplulimab, Drug: Second-Line Chemo/Targeted Therapy |
| Control Group | Active comparator | Drug: Second-Line Chemo/Targeted Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥18 years, male or female. Histologically confirmed early relapse (within 1 year after surgery, UICC stage IV) of colorectal cancer after adjuvant chemotherapy, with initially unresectable metastatic lesions or refusal of surgery.
- Have received standard postoperative adjuvant chemotherapy (XELOX or FOLFOX). Before enrollment, tumor tissue tested by immunohistochemistry as pMMR, or by PCR or NGS as MSS or MSI-L.
- At least one measurable tumor lesion according to RECIST 1.1 criteria. ECOG performance status 0-1. Life expectancy ≥3 months.
- Neutrophils ≥1.5 × 10⁹/L; platelets ≥100 × 10⁹/L; hemoglobin ≥9 g/dL; serum albumin ≥3 g/dL.
- Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN), with T3 and T4 within normal range.
Key exclusion criteria (9 listed)
- Pathologically diagnosed other intestinal tumors, such as gastrointestinal stromal tumors.
- RAS mutation status not tested. Tumor tissue tested by immunohistochemistry as dMMR, or by PCR or NGS as MSI-H. Metastatic lesions are resectable, or the patient wishes to undergo metastasectomy.
- Uncontrolled active bleeding from the primary tumor or intestinal obstruction. Contraindications to immune checkpoint inhibitor therapy. Hypersensitivity to study drugs or their excipients. Prior or concurrent other malignancy, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma.
- Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); excluding autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone, type I diabetes mellitus treated with stable doses of insulin, vitiligo, or childhood asthma/allergy that has resolved and requires no intervention in adulthood.
- History of immunodeficiency, including HIV positivity, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation.
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 |
|---|---|---|
| SerplulimabSerplulimab: 3 mg/kg intravenously on Day 1, repeated every 2 weeks | Drug | Experimental Group |
| Second-Line Chemo/Targeted TherapyLeft-sided, RAS wild-type Treatment Regimen: Cetuximab 400 mg/m², intravenous infusion, first infusion over >2 hours, then 250 mg/m² intravenous infusion over ≥60 minutes, repeated weekly; FOLFIRI: Irinotecan 180 mg/m², intravenous infusion over 90 minutes, Day 1; Leucovorin (LV) 400 mg/m², intravenous infusion over 2 hours, Day 1; 5-FU 400 mg/m², intravenous bolus, Day 1; followed by 2400 mg/m² infusion over 46-48 hours; Repeated every 2 weeks Right-sided, RAS mutant Treatment Regimen: Bevacizumab 5 mg/kg, intravenous infusion, Day 1, repeated every 2 weeks FOLFIRI: Irinotecan 180 mg/m², intravenous infusion over 90 minutes, Day 1; Leucovorin (LV) 400 mg/m², intravenous infusion over 2 hours, Day 1; 5-FU 400 mg/m², intravenous bolus, Day 1; followed by 2400 mg/m² infusion over 46-48 hours; Repeated every 2 weeks | Drug | Control Group, Experimental Group |
Primary outcome
Progression-free survival (PFS)
Time frame: 12 months
Progression-free survival (PFS) is defined as the time from randomization to the first documented tumor progression or death from any cause.
4 secondary outcomes
Objective response rate (ORR = CR + PR)
Time frame: 12 months
Disease control rate (DCR = CR + PR + SD)
Time frame: 12 months
R0 resection rate
Time frame: 12 months
Overall survival (OS)
Time frame: 36 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 22 May 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 Serplulimab and Second-Line Chemo/Targeted Therapy in people with Colorectal Cancer and Relapse, 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 12 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: looking for participants now, as of the sponsor's last update on 22 May 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 Qingguo Li, M.D. (+86-18918298120, qingguoli@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: 12 months). 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 22 May 2026; AzTrials last refreshed its copy on 4 Nov 2026.