Short-Term Radiotherapy Combined With Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX Neoadjuvant Therapy for Locally Advanced Rectal Cancer：A Multicenter, Prospective, Randomized, Phase II Clinical Trial
This study is a multicenter, prospective, randomized, double-arm, Phase II clinical trial designed to evaluate the efficacy of short-term radiotherapy combined with Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as neoadjuvant therapy for locally advanced rectal cancer. Additionally, the study seeks to explore the relationship between biomarkers in blood, urine, feces, and tumor tissue and treatment efficacy. Eligible participants (pMMR/MSS locally advanced rectal cancer) were randomly assigned in a 1:1 ratio to two groups, with randomization stratified by MRF (+ vs. -). Participants will: * Group A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy. * Group B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy. After two cycles of neoadjuvant therapy in Group A and six cycles in Group B, efficacy was evaluated and decisions regarding surgery or watchful waiting were made based on efficacy.
• Age: 18-75 years.
• Pathology: Histologically confirmed rectal adenocarcinoma, with the lower tumor edge ≤12 cm from the anal verge.
• Initial Clinical Stage: cT3-4aN0M0 or cT1-4aN+M0, regardless of MRF, EMVI, or LLNM status.
• Preoperative staging methods: chest and abdominal CT, pelvic MRI, endoscopic ultrasound (EUS), or transrectal ultrasonography.
• pMMR/MSS Status: pMMR confirmed by immunohistochemistry (IHC) at the study center's pathology department, or MSS/MSI-L confirmed by PCR or NGS.
• ECOG Performance Status: 0-1.
• Informed Consent: Voluntarily agrees to participate and signs the informed consent form.
• No Prior Treatment: No previous therapy targeting rectal adenocarcinoma, including radiotherapy, chemotherapy, or surgery.
• Planned Surgery: Surgery is planned upon completion of neoadjuvant therapy.
• Expected Survival: ≥6 months.
⁃ Adequate Organ and Bone Marrow Function, meeting all of the following (with no blood products, growth factors, or other hematopoietic-supportive medications used within 14 days before first administration):
⁃ Hematology:
⁃ Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L Platelet count ≥100 × 10\^9/L Hemoglobin ≥90 g/L
⁃ Serum Biochemistry:
⁃ Serum albumin ≥30 g/L Total bilirubin ≤1.5 × ULN ALT ≤2.5 × ULN, AST ≤2.5 × ULN Alkaline phosphatase (ALP) ≤2.5 × ULN
⁃ Serum creatinine ≤1.5 × ULN, or creatinine clearance (CrCl) ≥50 mL/min, calculated by the Cockcroft-Gault formula:
⁃ Contraception:
⁃ Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study dose, and must use effective contraception (e.g., intrauterine device, oral contraceptive, or barrier method) during the study and for at least 120 days after the final dose.
⁃ Male participants with partners of childbearing potential must be surgically sterile or must agree to use effective contraception during the study and for 120 days after the final dose.
⁃ Compliance and Follow-up: Demonstrates good compliance and agrees to attend follow-up visits.
⁃ Biological Samples: Agrees to provide blood, urine, stool, and tumor tissue samples.