pMMR/MSSPhase 2NCT07779694
16-Hour Fasting Plus Serplulimab and CAPEOX as Neoadjuvant Therapy in pMMR/MSS Advanced Mid-to-Low Rectal Cancer
A Phase 2 study testing 16-Hour Fasting and Serplulimab + chemotherapy in people with pMMR/MSS and Locally Advanced Rectal Carcinoma, run by Zhejiang University.
Trial summary
Although standard neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) effectively reduces local recurrence, radiotherapy-related toxicities and surgical complications severely impair patients' quality of life, making a radiotherapy-free strategy urgently needed. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- pMMR/MSS, Locally Advanced Rectal Carcinoma, Fasting, Intermittent
- What is being tested?
- 16-Hour Fasting and Serplulimab + chemotherapy
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 31 Dec 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent.
- Male or female subjects ≧ 18 years ≦ 75 of age.
- Histological or cytological documentation of adenocarcinoma of the rectum.
- No previous any systemic anticancer therapy for rectal cancer disease.
- The primary rectal tumor is assessed as likely to be R0 resectable by a multidisciplinary colorectal cancer collaborative team, comprising at least 2 gastrointestinal surgeons and 1 radiologist.
- The lower margin of the tumor is less than 10cm from the anus verge.
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- cT2N1-2M0, cT3N0-2M0, cT4N0-1M0 MSS with MRF(-) assessed by MRI.
- Primary tumor can be detected by CT or MRI.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Eligible tumor tissues were identified for MSI/MMR assays.
- Hepatitis B Surface Antigen (HBsAg) (-).
- If HBsAg (+) , HBV-DNA must be less than 2500 copies/mL or 500 IU/mL to be enrolled.
- Patients with HCV antibody (-) or HCV-RNA negative can be enrolled. Aspartate aminotransferase (AST) must be ≤ 3 x ULN for the lab. If HCV-RNA is positive, patients with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) performed ≤3×ULN could be enrolled. Patients infected with both hepatitis B virus and hepatitis C virus should be excluded (positive for HBsAg or HBcAb and positive for HCV antibodies).
Who cannot join
- Patients with recurrent rectal cancer or a history of pelvic radiotherapy.
- Patients with a history of inflammatory bowel disease.
- Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease (HIV1 antibody, HIV2 antibody, HTLV1 antibody positive) should be excluded.
- Patients who are preparing for or have previously received an organ or bone marrow transplant.
- History of myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥470 ms in women) in the 6 months prior to enrollment (QTc interval calculated by Fridericia formula).
- According to New York College of Cardiology (NYHA) standards for Grade III-IV cardiac insufficiency or cardiac color ultrasound: left ventricular ejection fraction (LVEF) <50%.Poor hypertension control (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.
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- Poor hypertension control (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.
- Patients had undergone major surgery within 28 days prior to enrollment. Patients with tumor biopsy or lymph node dissection biopsy were admitted. Patients undergoing enterostomy due to intestinal obstruction were admitted.
- The patients had previously been treated with other antibodies/drugs that target immune checkpoints, such as PD-1, PD-L1, and cytotoxic T lymphocyte-associated Antigen 4 (CTLA-4).
- Patients are participating in other clinical studies, or plan to start this study treatment less than 14 days from the end of the previous clinical study.
- Uncontrolled tumor-related pain.
- A known history of severe allergy to any monoclonal antibody.
- Known to be allergic or intolerance to any oxaliplatin and capecitabine ingredients.
- Pregnant or lactating women.
- The investigators determined that the patient had other factors that might have led to the early termination of the study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Neoadjuvant 16-Hour Fasting Combined With Serplulimab and CAPEOX for pMMR/MSS Locally Advanced Mid-to-Low Rectal Cancer: A Prospective, Single-Arm, Phase II Trial.
Although standard neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) effectively reduces local recurrence, radiotherapy-related toxicities and surgical complications severely impair patients' quality of life, making a radiotherapy-free strategy urgently needed. However, chemotherapy alone yields a pathological complete response (pCR) rate of only 6.6%-15%, which is far from satisfactory.
The pMMR/MSS subtype, accounting for 90% of rectal cancers, is "immune-cold" and shows almost no response to PD-1 monotherapy; nonetheless, chemotherapy can reshape the tumor immune microenvironment, and multiple studies have demonstrated that combining chemotherapy with PD-1 inhibitors (without radiotherapy) can elevate pCR rates to 26.8%-42.9%, yet further improvement remains desirable. A recent mechanistic study published in Cell Metabolism (2026) revealed that a single 16-hour fasting episode before treatment promotes isoleucine accumulation in the tumor microenvironment, which enhances CD8+T-cell cytotoxic function and reduces exhaustion through acetyl-CoA metabolism and epigenetic reprogramming, thereby significantly sensitizing PD-1 inhibitors-and this intervention is non-invasive, low-cost, and easily adoptable by patients.
Based on the above evidence, we hypothesize that the neoadjuvant triple-combination regimen of "16-hour fasting + chemotherapy + PD-1 inhibitor" (radiotherapy-free) in pMMR/MSS locally advanced mid-to-low rectal cancer may further increase pCR rates and tumor regression, offering a novel, highly effective, and low-toxicity therapeutic option for LARC patients.
- Being tested
- 16-Hour Fasting, Serplulimab + chemotherapy
- Keywords
- Rectal cancer, Serplulimab, CAPEOX, neoadjuvant therapy, 16-hour fasting
- Medical subject headings
- Intermittent Fasting, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
16-Hour FastingBehavioural
Patients begin fasting at 20:00 on the day prior to immunotherapy (only plain water is allowed) and continue until 10:00 the next morning, when serplulimab is administered. Fasting is maintained until 12:00 noon, after which normal diet may be resumed.
Serplulimab + chemotherapyDrug
Serplulimab is an innovative monoclonal antibody targeting PD-1, developed by Shanghai Henlius Biotech, Inc. 300 mg, IV, d1, q3w.
CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w.
4 cycles
| Study group | Role | What they receive |
|---|---|---|
| 16-Hour Fasting + Serplulimab + CAPEOX | Experimental | Patients enrolled in the study are required to fast for 16 hours prior to the administration of serplulimab in combination with CAPEOX.
Serplulimab: 300 mg, IV, d1, q3w. CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w.
Treatment repeats every 3 weeks for 4 cycles followed by surgery (total mesorectal excision, TME). Receives: Behavioral: 16-Hour Fasting; Drug: Serplulimab + chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response rates
Proportion of participants achieving pathological complete response (pCR) after neoadjuvant therapy.
Measured: 10 days after surgery
Secondary outcomes (8)
Rate of clinical complete response rate(cCR)
Proportion of participants achieving clinical complete response (cCR) after neoadjuvant therapy.
Measured: 1 year
R0 resection rates
Proportion of patients achieved a complete resection with negative margin
Measured: 10 days after surgery
Disease Free Survival
Defined as the interval from enrollment to locoregional or metastatic recurrence or the appearance or a secondary colorectal cancer or death, whichever occurs first
Measured: 3 years
Event free survival
Defined as the time from enrollment to the first occurrence of any of the following events: tumor disease progression on imaging as assessed by RECIST 1.1; tumor recurrence, including local recurrence or distant recurrence, as assessed on imaging or tissue biopsy transfer; death from any cause.
Measured: 3 years
Overall survival (OS)
Defined as the time between the date of enrollment and death from any cause.
Measured: 3 years
Treatment-related adverse events
Assessed by evaluation of treatment-related adverse events.
Measured: 1 year
Single-Cell RNA Sequencing (scRNA-seq) of Tumor Microenvironment
Use single cell sequence to describe changes in the microenvironment of rectal cancer before and after treatment.
Measured: 1 year
Spatial Transcriptomics Profiling of Tumor and Stroma
Explore spatial organization of gene expression within the tumor microenvironment and its association with treatment response using spatial transcriptomics.
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 posted21 Aug 2026
- Study start1 Oct 2026 (estimated)
- Primary completion31 Dec 2028 (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 pMMR/MSSStudies of the same condition, open and under way.
- More trials run by Zhejiang 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ding Ke-Feng, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07779694
- Sponsor's protocol ID
- SCAR2
- Status last verified
- Aug 2026
- First submitted
- 18 Aug 2026
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- 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 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant 16-Hour Fasting Combined With Serplulimab and CAPEOX for pMMR/MSS Locally Advanced Mid-to-Low Rectal Cancer: A Prospective, Single-Arm, Phase II Trial.
- ClinicalTrials.gov ID
- NCT07779694
- Acronym / sponsor ID
- SCAR2
- Keywords
- Rectal cancer, Serplulimab, CAPEOX, neoadjuvant therapy, 16-hour fasting
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Zhejiang UniversityUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 21 Aug 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.
Although standard neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) effectively reduces local recurrence, radiotherapy-related toxicities and surgical complications severely impair patients' quality of life, making a radiotherapy-free strategy urgently needed. However, chemotherapy alone yields a pathological complete response (pCR) rate of only 6.6%-15%, which is far from satisfactory.
The pMMR/MSS subtype, accounting for 90% of rectal cancers, is "immune-cold" and shows almost no response to PD-1 monotherapy; nonetheless, chemotherapy can reshape the tumor immune microenvironment, and multiple studies have demonstrated that combining chemotherapy with PD-1 inhibitors (without radiotherapy) can elevate pCR rates to 26.8%-42.9%, yet further improvement remains desirable. A recent mechanistic study published in Cell Metabolism (2026) revealed that a single 16-hour fasting episode before treatment promotes isoleucine accumulation in the tumor microenvironment, which enhances CD8+T-cell cytotoxic function and reduces exhaustion through acetyl-CoA metabolism and epigenetic reprogramming, thereby significantly sensitizing PD-1 inhibitors-and this intervention is non-invasive, low-cost, and easily adoptable by patients.
Based on the above evidence, we hypothesize that the neoadjuvant triple-combination regimen of "16-hour fasting + chemotherapy + PD-1 inhibitor" (radiotherapy-free) in pMMR/MSS locally advanced mid-to-low rectal cancer may further increase pCR rates and tumor regression, offering a novel, highly effective, and low-toxicity therapeutic option for LARC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 16-Hour Fasting + Serplulimab + CAPEOX | Experimental | Behavioral: 16-Hour Fasting, Drug: Serplulimab + chemotherapyPatients enrolled in the study are required to fast for 16 hours prior to the administration of serplulimab in combination with CAPEOX. Serplulimab: 300 mg, IV, d1, q3w. CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w. Treatment repeats every 3 weeks for 4 cycles followed by surgery (total mesorectal excision, TME). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Willing and able to provide written informed consent.
- Male or female subjects ≧ 18 years ≦ 75 of age.
- Histological or cytological documentation of adenocarcinoma of the rectum.
- No previous any systemic anticancer therapy for rectal cancer disease.
- The primary rectal tumor is assessed as likely to be R0 resectable by a multidisciplinary colorectal cancer collaborative team, comprising at least 2 gastrointestinal surgeons and 1 radiologist.
Key exclusion criteria (15 listed)
- Patients with recurrent rectal cancer or a history of pelvic radiotherapy.
- Patients with a history of inflammatory bowel disease.
- Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease (HIV1 antibody, HIV2 antibody, HTLV1 antibody positive) should be excluded.
- Patients who are preparing for or have previously received an organ or bone marrow transplant.
- History of myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥470 ms in women) in the 6 months prior to enrollment (QTc interval calculated by Fridericia formula).
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 |
|---|---|---|
| 16-Hour FastingPatients begin fasting at 20:00 on the day prior to immunotherapy (only plain water is allowed) and continue until 10:00 the next morning, when serplulimab is administered. Fasting is maintained until 12:00 noon, after which normal diet may be resumed. | Behavioural | 16-Hour Fasting + Serplulimab + CAPEOX |
| Serplulimab + chemotherapySerplulimab is an innovative monoclonal antibody targeting PD-1, developed by Shanghai Henlius Biotech, Inc. 300 mg, IV, d1, q3w. CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w. 4 cycles | Drug | 16-Hour Fasting + Serplulimab + CAPEOX |
Primary outcome
Pathological complete response rates
Time frame: 10 days after surgery
Proportion of participants achieving pathological complete response (pCR) after neoadjuvant therapy.
8 secondary outcomes
Rate of clinical complete response rate(cCR)
Time frame: 1 year
R0 resection rates
Time frame: 10 days after surgery
Disease Free Survival
Time frame: 3 years
Event free survival
Time frame: 3 years
Overall survival (OS)
Time frame: 3 years
Treatment-related adverse events
Time frame: 1 year
Single-Cell RNA Sequencing (scRNA-seq) of Tumor Microenvironment
Time frame: 1 year
Spatial Transcriptomics Profiling of Tumor and Stroma
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 8 Sep 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 16-Hour Fasting and Serplulimab + chemotherapy in people with pMMR/MSS and Locally Advanced Rectal Carcinoma, run by Zhejiang University.
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 13 inclusion and 15 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 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
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 feng Ke Ding (+86 13588425440, dingkefeng@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response rates (time frame: 10 days after surgery). 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 8 Sep 2026.