Chemotherapy With or Without Radiation and Serplulimab Before Surgery for Advanced Colon Cancer

Trial details

Who runs it

Fudan University

Trial code

NCT07877597

Record updated

16 October 2026

Original description

Locally advanced colon cancer, particularly T4 disease or colon cancer with bulky nodes, carries a poor prognosis and limited efficacy with neoadjuvant chemotherapy. In our previous small-sample phase II study, PD-1 inhibitor plus CAPOX chemotherapy combined with short-course radiotherapy yielded a marked improvement in the pCR rate compared with neoadjuvant CAPOX alone, though survival outcomes remain under follow-up. This prospective, multicentre, randomised, three-arm phase III study enrolls 480 patients with pMMR/MSS locally advanced high-risk colon cancer. Participants are randomised in a 2:2:1 ratio to three arms: short-course radiotherapy combined with chemotherapy and PD-1 inhibitor (25 Gy in 5 fractions of radiotherapy, followed by 4 cycles of CAPOX plus the PD-1 inhibitor serplulimab); chemotherapy plus PD-1 inhibitor (4 cycles of CAPOX combined with serplulimab); and chemotherapy alone (4 cycles of CAPOX). The primary endpoint is the 3-year event-free survival (EFS) rate. Secondary endpoints include the pCR rate, 5-year overall survival rate (5y OS), R0 resection rate, toxicity, surgical complications and quality of life.Read full original descriptionShow less

A Prospective, Randomized, Multicenter, Phase III Clinical Study of Chemotherapy Combined With or Without Short-Course Radiotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for High-Risk Locally Advanced Colon Cancer With pMMR/MSS (TORCH-C2 Trial)

Locally advanced colon cancer, particularly T4 disease or colon cancer with bulky nodes, carries a poor prognosis and limited efficacy with neoadjuvant chemotherapy. In our previous small-sample phase II study, PD-1 inhibitor plus CAPOX chemotherapy combined with short-course radiotherapy yielded a marked improvement in the pCR rate compared with neoadjuvant CAPOX alone, though survival outcomes remain under follow-up. This prospective, multicentre, randomised, three-arm phase III study enrolls 480 patients with pMMR/MSS locally advanced high-risk colon cancer. Participants are randomised in a 2:2:1 ratio to three arms: short-course radiotherapy combined with chemotherapy and PD-1 inhibitor (25 Gy in 5 fractions of radiotherapy, followed by 4 cycles of CAPOX plus the PD-1 inhibitor serplulimab); chemotherapy plus PD-1 inhibitor (4 cycles of CAPOX combined with serplulimab); and chemotherapy alone (4 cycles of CAPOX). The primary endpoint is the 3-year event-free survival (EFS) rate. Secondary endpoints include the pCR rate, 5-year overall survival rate (5y OS), R0 resection rate, toxicity, surgical complications and quality of life.

Inclusion: 1. Aged ≥18 years, of any gender. 2. Colon adenocarcinoma confirmed by histopathology, with the tumour located >15 cm from the anal verge on colonoscopy; Locally high-risk disease demonstrated by contrast-enhanced abdominal CT or MRI, defined as tumour invasion beyond the serosa or into adjacent organs (cT4), or high-risk lymph nodes and tumour deposits. No distant metastasis (M0) identified on chest CT plus contrast-enhanced pelvic CT/MRI, or whole-body PET-CT; pMMR or MSS status confirmed by immunohistochemistry or genetic testing. 5. No prior anti-tumour therapy. 6. ECOG performance status 0-1, with an expected survival of ≥3 months. Patients must be willing to cooperate with adverse event and efficacy assessments; Adequate organ function:; Neutrophils ≥1.5×10⁹/L; platelets ≥100×10⁹/L; haemoglobin ≥9 g/dL (or ≥9 g/dL after transfusion or supportive care); serum albumin ≥3 g/dL; Thyroid-stimulating hormone (TSH) ≤1×upper limit of normal (ULN), with T3 and T4 within normal ranges; Bilirubin ≤1.5×ULN; ALT and AST ≤2×ULN; Serum creatinine ≤1.5×ULN; creatinine clearance ≥60 mL/min; International normalised ratio (INR) or prothrombin time (PT) ≤1.5×ULN, unless the patient is on anticoagulation with PT within the expected therapeutic range of the anticoagulant; activated partial thromboplastin time (aPTT) ≤1.5×ULN; No severe concomitant disease that would limit life expectancy to less than 5 years; Female subjects of childbearing potential must have a negative pregnancy test; female subjects without childbearing potential are also eligible; Male patients of childbearing potential and female patients with childbearing potential and pregnancy risk must agree to use adequate contraception throughout the study period and for 12 months after completion of study treatment; Signed and dated informed consent form, indicating that the patient has been informed of all relevant aspects of the study; Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion: 1. Histopathological diagnosis of other colonic neoplasms, such as gastrointestinal stromal tumour, lymphoma, etc; Prior treatment with PD-1 antibody, PD-L1 antibody or CTLA-4 antibody. 3. Previous or concurrent malignancy, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and papillary thyroid carcinoma; Active autoimmune disease or a history of autoimmune disease (including but not limited to interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism and hypothyroidism). Exceptions include autoimmune-mediated hypothyroidism treated with a stable dose of thyroid replacement hormone; type 1 diabetes mellitus managed with stable-dose insulin; vitiligo; or childhood asthma/allergy that has resolved and requires no intervention in adulthood; History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency disorders, or a history of solid organ transplantation and allogeneic bone marrow transplantation; History of interstitial lung disease (excluding radiation pneumonitis not treated with steroids) or non-infectious pneumonitis; Subjects with active pulmonary tuberculosis identified by medical history or CT scan; those with a history of active pulmonary tuberculosis within 1 year prior to enrollment; or those with a history of active pulmonary tuberculosis more than 1 year previously who did not receive standard anti-tuberculosis treatment; Subjects with active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL) or hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of quantification of the assay); Severe impairment of cardiac, pulmonary, renal or hepatic function. 10. Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); History of psychoactive substance abuse, alcoholism or illicit drug use. 12. Other factors judged by the investigator to compromise subject safety or trial compliance. Examples include severe diseases requiring concomitant treatment (including psychiatric disorders), significant laboratory abnormalities, or other familial or social factors.

ClinicalTrials.gov NCT07877597