Locally Advanced Rectal Cancer
Conditions
Interventions
Intervention Group:Neoadjuvant Pucotenlimab in Combination with Chemoradiotherapy
Control Group:Neoadjuvant Chemoradiotherapy
Sponsors
Fuzhou University Affiliated Provincial Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Voluntarily participate in the study and provide signed written informed consent; 2.Aged 18-75 years, male or female; 3.Histologically or cytologically confirmed rectal adenocarcinoma, diagnosed as pMMR by immunohistochemistry on endoscopic biopsy specimens or as MSS by genetic testing (PCR or NGS). 4.Clinical stage T3-4N0M0 or TanyN+M0 (eligibility of T4 subjects must be confirmed by the enrollment steering committee), with the distal margin of the lesion located below the peritoneal reflection as confirmed by MRI, and assessed by the investigator as anticipated to achieve an R0 resection; 5.No prior systematic anti-tumor therapy (including systemic chemotherapy, radiotherapy, molecular targeted therapy, immunotherapy, biotherapy, local therapy, or any other investigational drugs). 6.At least one measurable lesion according to RECIST 1.1 (lesion with longest diameter >=10 mm); 7.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 8.Planned to undergo surgical resection after completion of neoadjuvant therapy; 9.Life expectancy >=12 weeks; 10.Adequate organ and hematopoietic function, without blood transfusion or use of any hematopoietic growth factors within 14 days prior to the first dose of the study drug, based on the following laboratory values: Neutrophil count >=1.5×10^9/L; Platelet count >=100×10^9/L. Hemoglobin >=90 g/L. Serum creatinine <=1.5 × upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5 × ULN. Total bilirubin (TBIL) <=1.5 × ULN. International normalized ratio (INR) <=1.5 × ULN, and activated partial thromboplastin time (APTT) <=1.5 × ULN (except for patients receiving anticoagulant therapy); 11.Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment. Both female patients of childbearing potential and male patients with partners of childbearing potential must agree to use highly effective contraceptive methods (e.g., oral contraceptives, intrauterine device, sexual abstinence, or barrier methods combined with spermicide) from signing the informed consent form until one year after the last dose of the study drug.
Exclusion criteria
Exclusion criteria: 1.History of other primary malignancies. Note: Except for adequately treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Patients with other malignancies who have undergone radical therapy and have been disease-free for 5 years may be enrolled; 2.Histologically or cytologically confirmed undifferentiated carcinoma, squamous cell carcinoma, or mixed type carcinoma; 3.Presence of synchronous colorectal cancer; 4.Anatomically defined anal canal cancer or rectal cancer with the distal margin located above the peritoneal reflection; 5.History of severe cardiac dysfunction, stroke, or transient ischemic attack (TIA) within 6 months prior to enrollment. History of ventricular tachycardia or torsades de pointes. Any clinically significant abnormalities in rhythm, conduction, or morphology on resting ECG, e.g., QTcF >450 ms for males or >470 ms for females, complete left bundle branch block, or third-degree atrioventricular block. Clinically significant heart disease, including acute myocardial infarction occurring within 6 months prior to the first study treatment, Class III or IV congestive heart failure (New York Heart Association classification), unstable angina, or arrhythmia requiring medication. Note: Patients with arrhythmia receiving antiarrhythmic medication and showing controlled heart rhythm on screening ECG may be enrolled; 6.History of pulmonary embolism or deep vein thrombosis within 3 months prior to signing informed consent; 7.Uncontrolled or poorly controlled hypertension (e.g., systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) or hyperglycemia; 8.Active bleeding, history of coagulation disorders, or patients receiving coumarin anticoagulant therapy; 9.Complete intestinal obstruction or subjects at potential risk of obstruction (e.g., presenting with symptoms including, but not limited to, cessation of flatus and defecation), or subjects suspected of intestinal perforation based on clinical symptoms or imaging; 10.Known allergy to pucotenlimab or any other investigational drug(s) used in this study or their components; 11.Known active Hepatitis B or C. ? Active Hepatitis B is defined as HBsAg positive and HBV DNA >=500 IU/mL. ? Active Hepatitis C is defined as known positive Hepatitis C antibody and known quantitative HCV RNA results above the lower limit of detection. ? Presence of other severe liver diseases, including chronic autoimmune liver disease, primary biliary cholangitis or sclerosing cholangitis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH); 12.Active infection requiring continuous antibiotic therapy within 4 weeks prior to randomization (CTCAE >=Grade 2), or known HIV infection (HIV antibody positive), or a diagnosis of AIDS. 13.Administration of a live virus vaccine within 4 weeks prior to randomization. Inactivated seasonal influenza vaccines are permitted; 14.Major surgery within 4 weeks prior to randomization without full recovery; 15.History of or current interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc., or active tuberculosis or history of tuberculosis within 12 months prior to randomization; 16.Uncontrolled autoimmune disease, or active autoimmune disease requiring immunosuppressants and/or systemic corticosteroid therapy (>10 mg/day prednisone or equivalent) within 2 weeks prior to randomiz
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Response (CR) Rate: The proportion of patients achieving pathological complete response (pCR) or sustained clinical complete response (cCR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Tumor Regression Grade;Event-Free Survival (EFS);Safety Endpoints: Analysis of adverse events (AEs) and serious adverse events (SAEs);Resectability Rate, R0 Resection Rate;Overall Survival (OS); | — |
Countries
China
Contacts
Public ContactFangqin Xue
Fuzhou University Affiliated Provincial Hospital
Outcome results
None listed