A Phase 3 interventional study of Serplulimab and FOLFOXIRI chemotherapy in Locally Advanced Low Rectal Adenocarcinoma and pMMR (Microsatellite Stable Rectal Cancer), sponsored by Sun Yat-sen University. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-12-11.
Sponsored by Sun Yat-sen University · Phase 3, Interventional, and Treatment
The goal of this clinical trial is to find out if adding a PD-1 antibody (serplulimab) to FOLFOXIRI chemotherapy and radiotherapy works better than CAPOX chemotherapy with radiotherapy as total neoadjuvant therapy for adults with pMMR locally advanced low rectal cancer. It will also look at the safety of these treatments and how they affect long-term outcomes such as organ preservation and survival.
The main questions it aims to answer are:
Does PD-1 antibody plus FOLFOXIRI with radiotherapy improve 3-year event-free survival compared with CAPOX with radiotherapy?
Does this treatment increase the chance of clinical complete response and avoiding a permanent stoma (sphincter-preserving or non-surgical "watch-and-wait" management)?
What side effects and medical problems occur during and after these treatments?
Researchers will compare:
Group A (experimental group): PD-1 antibody (serplulimab) plus FOLFOXIRI chemotherapy combined with long-course radiotherapy as total neoadjuvant therapy.
Group B (control group): CAPOX chemotherapy combined with long-course radiotherapy as total neoadjuvant therapy.
Participants will:
Sign an informed consent form and have screening tests (physical exam, blood tests, ECG, imaging such as MRI/CT, endoscopy) to confirm they can join the trial.
Be randomly assigned (like drawing lots) to Group A or Group B. Receive several cycles of chemotherapy together with a 5-week course of pelvic radiotherapy before surgery; the experimental group will also receive PD-1 antibody during part of the chemotherapy and radiotherapy period.
Have regular clinic visits for checkups, blood tests, and assessment of side effects during treatment.
After neoadjuvant therapy, have MRI/CT and endoscopy to assess tumor response. Depending on the response, they may:
Receive surgery to remove the rectal tumor, or
If a clinical complete response is achieved and both doctor and patient agree, enter a "watch-and-wait" program instead of immediate surgery.
Provide blood samples and allow tumor tissue to be collected (for example, from biopsy and surgery) for future research (such as building PDX models and testing blood markers).
Be followed regularly for at least 5 years with clinic visits, blood tests (including CEA), imaging, and colonoscopy to check for tumor recurrence, side effects, and quality of life.
Sun Yat-sen University is the lead sponsor of 1,644 studies on the registry; 602 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants in this arm will receive a PD-1 antibody (serplulimab) in combination with FOLFOXIRI chemotherapy and long-course pelvic radiotherapy as total neoadjuvant therapy before surgery. Treatment will be given according to the study protocol, with regular safety monitoring and response assessments.
Drug: Serplulimab · Drug: FOLFOXIRI chemotherapy · Radiation: Long-course pelvic radiotherapy
Participants in this arm will receive CAPOX chemotherapy and long-course pelvic radiotherapy as total neoadjuvant therapy before surgery. Treatment will be given according to the study protocol, with regular safety monitoring and response assessments.
Drug: CAPOX chemotherapy · Radiation: Long-course pelvic radiotherapy
Serplulimab will be administered intravenously in combination with FOLFOXIRI chemotherapy and long-course pelvic radiotherapy as part of total neoadjuvant therapy in the experimental arm.
Also known as: PD-1 antibody
The FOLFOXIRI chemotherapy regimen (5-fluorouracil, leucovorin, oxaliplatin, irinotecan) will be administered according to the study protocol as part of total neoadjuvant therapy in the experimental arm, in combination with serplulimab and long-course pelvic radiotherapy.
Also known as: 5-fluorouracil, leucovorin, oxaliplatin, irinotecan
The CAPOX chemotherapy regimen (capecitabine plus oxaliplatin) will be administered according to the study protocol as part of total neoadjuvant therapy in the active comparator arm, in combination with long-course pelvic radiotherapy.
Also known as: Capecitabine plus oxaliplatin
Long-course pelvic external beam radiotherapy will be delivered according to institutional standards as part of total neoadjuvant therapy in both study arms, in combination with chemotherapy (FOLFOXIRI plus serplulimab in the experimental arm or CAPOX in the active comparator arm).
Also known as: External beam radiotherapy, Pelvic radiotherapy
3-year Event-Free Survival (EFS)
Event-free survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: (1) locoregional failure, including unresectable primary tumor after completion of total neoadjuvant therapy, R2 resection (macroscopic residual tumor), or local bed recurrence after R0-R1 resection; (2) distant metastasis; (3) new invasive primary colorectal cancer; or (4) death from any cause. Patients without an event at the time of analysis will be censored at the date of the last tumor assessment.
Time frame: Up to 3 years after randomization
Clinical Complete Response (cCR) Rate
Proportion of participants achieving clinical complete response (cCR) after completion of total neoadjuvant therapy. cCR will be assessed by digital rectal examination, endoscopy, pelvic MRI and serum CEA according to predefined criteria (no palpable tumor, endoscopic whitening or telangiectasia only, fibrotic signal on MRI without residual tumor or nodes, and normal CEA).
Time frame: At 10-14 weeks after completion of radiotherapy (response assessment prior to definitive management)
Anal Sphincter Preservation Rate
Proportion of participants who achieve anal sphincter preservation, defined as undergoing sphincter-preserving surgery (e.g., low anterior resection, intersphincteric resection) or managed with a watch-and-wait strategy without permanent stoma at last follow-up.
Time frame: From randomization to definitive management (surgery or decision for watch-and-wait) and last follow-up, up to approximately 1 year after randomization
Incidence of Treatment-related Adverse Events During Total Neoadjuvant Therapy
Number and proportion of participants experiencing treatment-related adverse events during total neoadjuvant therapy, graded according to NCI-CTCAE version 5.0. Both overall adverse events and grade 3-5 toxicities related to chemotherapy, immunotherapy, or radiotherapy will be summarized.
Time frame: From first dose of study treatment until 30-90 days after completion of chemotherapy/radiotherapy or surgery, up to approximately 1 year after randomization
Plan to share: No
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Sun Yat-sen University