Colorectal Cancer (Locally Advanced or Metastatic)Phase 4NCT07446465
FOLFOX Chemotherapy Combined With Fruquintinib and Serplulimab as First-Line Conversion Therapy for Initially Unresectable pMMR/MSS Colorectal Cancer
A Phase 4 study testing Serplulimab, Fruquintinib and mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU) in people with Colorectal Cancer (Locally Advanced or Metastatic) and Colorectal Cancer Microsatellite Stable (MSS), run by Ye Xu at 1 site in China.
Trial summary
To evaluate the efficacy and safety of immune checkpoint inhibitor-based combination therapy with targeted therapy and chemotherapy in patients with locally advanced unresectable or metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer (Locally Advanced or Metastatic), Colorectal Cancer Microsatellite Stable (MSS)
- What is being tested?
- Serplulimab, Fruquintinib and mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2026to 31 Jan 2027
- Phase
- Phase 4
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;
- Histologically confirmed adenocarcinoma of colorectal cancer, initially unresectable locally advanced or metastatic/recurrent disease;
- Expected survival ≥12 weeks;
- No prior systemic antitumor therapy for colorectal cancer;
- Confirmed pMMR by IHC or MSS/MSI-L by PCR or NGS;
- ECOG PS 0-1;
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- At least one measurable lesion per RECIST v1.1;
- Adequate organ and bone marrow function;
- Controlled viral hepatitis status as specified;
- Signed written informed consent.
Who cannot join
- Prior immune checkpoint inhibitor therapy;
- CNS or leptomeningeal metastases;
- Uncontrolled cardiovascular disease or hypertension;
- Active autoimmune disease requiring systemic therapy;
- Active infection including tuberculosis;
- Recent major surgery;
- Pregnancy or lactation;
- Any condition deemed by investigators to compromise safety or study compliance.
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
Fudan University Shanghai Cancer Center
Shanghai, Xuhui
Ye Xu, +86 18017312565, yexu@shmu.edu.cn
About this study
Official title: Exploratory Clinical Study of FOLFOX Chemotherapy Combined With Fruquintinib and Serplulimab as First-Line Conversion Therapy for Initially Unresectable pMMR/MSS Colorectal Cancer
To evaluate the efficacy and safety of immune checkpoint inhibitor-based combination therapy with targeted therapy and chemotherapy in patients with locally advanced unresectable or metastatic colorectal cancer.
Read the detailed description
1.1 Overview of Colorectal Cancer Colorectal cancer (CRC) is the third most common malignancy worldwide and a leading cause of cancer-related mortality. In China, CRC incidence and mortality continue to rise, with a high proportion of patients diagnosed at advanced stages. While radical surgery remains the cornerstone of curative treatment, many patients present with unresectable disease, and long-term survival remains poor.
Immune checkpoint inhibitors targeting PD-1/PD-L1 have transformed cancer therapy; however, their benefit in CRC is largely confined to dMMR/MSI-H tumors, which account for only 10-15% of cases. The majority of CRC patients with pMMR/MSS disease derive little benefit from immunotherapy alone.
1.2 Conversion Therapy in Colorectal Cancer Conversion therapy aims to downstage initially unresectable tumors through systemic treatment, enabling surgical resection. In metastatic CRC, successful conversion followed by radical resection can significantly improve long-term survival, with 5-year survival rates reaching 30-50% in selected patients.
1.3 Immunotherapy and Targeted Therapy in pMMR/MSS CRC pMMR/MSS tumors are considered "cold tumors" with low tumor mutational burden and limited immune cell infiltration. Multiple trials have shown minimal efficacy of PD-1 inhibitors alone in this population. Combination strategies incorporating chemotherapy and anti-angiogenic agents may enhance immune response and improve outcomes.
1.4 Serplulimab Serplulimab is a fully humanized anti-PD-1 IgG4 monoclonal antibody with high affinity, slow dissociation, low immunogenicity, and favorable safety characteristics. It has been approved in China for multiple indications including lung cancer and esophageal squamous cell carcinoma, with demonstrated survival benefits.
1.5 Fruquintinib Fruquintinib is a highly selective small-molecule VEGFR inhibitor targeting VEGFR-1, -2, and -3. It inhibits tumor angiogenesis with high potency and manageable toxicity. Fruquintinib has been approved for metastatic colorectal cancer refractory to standard therapies.
1.6 Rationale for This Study Based on strong preclinical and clinical evidence supporting the synergistic effects of immunotherapy, anti-angiogenic therapy, and chemotherapy, this study is the first to explore serplulimab combined with fruquintinib and FOLFOX chemotherapy as first-line conversion therapy in pMMR/MSS colorectal cancer.
- Conditions
- Colorectal Cancer (Locally Advanced or Metastatic), Colorectal Cancer Microsatellite Stable (MSS)
- Being tested
- Serplulimab, Fruquintinib, mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU)
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SerplulimabDrug
Serplulimab: 200 mg IV Day 1, q2w
FruquintinibDrug
Fruquintinib: 4 mg orally once daily, Days 1-21, every 4 weeks
mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU)Drug
Oxaliplatin 85 mg/m² IV q2w Leucovorin 400 mg/m² IV q2w 5-FU 400 mg/m² IV bolus Day 1 5-FU 1200 mg/m²/day continuous IV infusion Days 2-3
| Study group | Role | What they receive |
|---|---|---|
| Conversion Therapy | Experimental | Conversion Therapy (≤6 months) Fruquintinib: 4 mg orally once daily, Days 1-21, every 4 weeks mFOLFOX6: Oxaliplatin 85 mg/m² IV q2w Leucovorin 400 mg/m² IV q2w 5-FU 400 mg/m² IV bolus Day 1 5-FU 1200 mg/m²/day continuous IV infusion Days 2-3 Serplulimab: 200 mg IV Day 1, q2w Fruquintinib must be stopped ≥2 weeks prior to surgery and resumed ≥4 weeks postoperatively. Receives: Drug: Serplulimab; Drug: Fruquintinib; Drug: mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conversion Rate to Surgery
Measured: ≤ 6 months
Objective Response Rate
Measured: ≤6 month
Secondary outcomes (6)
Disease Control Rate
Measured: 6 months
Depth of Response
Depth of Response (DpR): defined as the maximum percentage reduction of tumor target lesions compared with baseline (pre-treatment) during the course of tumor treatment.
Measured: 6 months
Early Tumor Shrinkage
Early Tumor Shrinkage (ETS): defined as a predefined percentage reduction in the sum of the longest diameters of target lesions within a specified time period after the initiation of treatment.
Measured: 6 months
R0 Resection Rate
Measured: 6 months
Progression-Free Survival
Measured: 6 months
Overall Survival
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2026
- Study start1 Mar 2026 (estimated)
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer (Locally Advanced or Metastatic)Studies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ye Xu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ye Xu, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07446465
- Sponsor's protocol ID
- FRUTISCO
- Status last verified
- Feb 2026
- First submitted
- 24 Feb 2026
- Last updated
- 3 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes