Yang et al. Anti-PD-1/CTLA-4 Dual Immunotherapy for LARC

Starting soon · Phase 2/Phase 3

Conditions studied: Locally Advanced Rectal Adenocarcinoma, Neoadjuvant Chemoradiation, Neoadjuvant Immunotherapy

In brief

This is a prospective, multicenter, randomized controlled trial aimed at comparing different radiotherapy fractionation regimens combined with sequential dual immunotherapy versus traditional chemoradiotherapy in neoadjuvant treatment for locally advanced rectal cancer (LARC). A total of 342 pMMR/MSS LARC patients will be enrolled and randomly assigned in a 1:1:1 ratio to short-course radiotherapy (5×5Gy) followed by sequential dual immunotherapy (paromlimab + tuvonralimab + CAPEOX), long-course radiotherapy followed by sequential dual immunotherapy, or conventional long-course chemoradiotherapy. The primary endpoint is the complete response rate (pCR + cCR). Secondary endpoints include the proportion of patients adopting the "watch-and-wait" strategy, disease-free survival, overall survival, and safety. This study innovatively explores the synergistic mechanism of different radiotherapy fractionations with dual immunotherapy, optimizes the timing of immunotherapy initiation, and constructs a clinical-imaging-pathology multimodal efficacy prediction model, aiming to advance LARC treatment from empirical to precision therapy while achieving organ and function preservation.

Key facts

Study ID

NCT07596290

Run by

Beijing Friendship Hospital

People needed

342

Starts

2026-07-15

Expected to finish

2030-12-31

Last updated by the study team

2026-06-17

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age between 18 and 80 years; ECOG performance status 0-1;
• Histopathologically confirmed rectal adenocarcinoma via colonoscopy; pMMR or MSS phenotype;
• Rectal MRI stage II/III (excluding T4b); distal tumor margin ≤ 12 cm from the anal verge;
• Willingness to comply with study procedures; consent to use tissue and blood samples for medical research purposes;
• No prior history of radiotherapy, chemotherapy, or immunotherapy;
• No immune system diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, hyperthyroidism/hypothyroidism, ulcerative colitis, autoimmune hemolytic anemia, HIV infection, etc.);
• No severe cardiac, pulmonary, hepatic, or renal dysfunction; no jaundice or gastrointestinal obstruction;
• No concurrent acute infection;
• Baseline laboratory evaluations completed as required, with results obtained within 14 days before randomization, and laboratory values meeting the following criteria (per CTCAE 5.0):
• White blood cell count ≥ 2000/μL;
• Neutrophil count ≥ 1500/μL;
• Platelet count ≥ 100×10³/μL;
• Hemoglobin ≥ 9.0 g/dL;
• Serum creatinine ≤ 1.5×upper limit of normal (ULN) or creatinine clearance > 50 mL/min (female: creatinine clearance = [140 - age (years)] × body weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)); male: creatinine clearance = [140 - age (years)] × body weight (kg) × 1.00 / (72 × serum creatinine (mg/dL)));
• AST ≤ 3×ULN, ALT ≤ 3×ULN, total bilirubin ≤ 1.5×ULN;
• No psychiatric/psychological disorders affecting social function;
• Negative serum pregnancy test (blood HCG) within 1 week before randomization for women of childbearing potential;
• Women of childbearing potential must agree to use effective contraception during the study period and for 5 months after the last dose of study drug;
• Male subjects who are sexually active with women of childbearing potential must agree to use effective contraception during the study period and for 7 months after the last dose of study drug, and must refrain from sperm donation during this period.

You may not qualify if…

• Multiple primary cancers or concurrent other malignant tumors;
• Patients requiring emergency surgery due to intestinal obstruction, intestinal perforation, gastrointestinal bleeding, etc.;
• Factors affecting oral drug absorption (e.g., inability to swallow, nausea/vomiting, diarrhea, intestinal obstruction, etc.);
• Any uncontrolled, severe concomitant diseases;
• Hypersensitivity to any component of the study drugs;
• Expected survival < 5 years for any reason;
• Planned or previous organ/bone marrow transplantation;
• Treatment with immunosuppressants or corticosteroids within 1 month before enrollment;
• Central nervous system disorders that may impair ability to provide informed consent or comply with study procedures, as determined by the investigator;
• Other conditions that may prevent completion of study treatment (e.g., alcoholism, drug addiction, etc.);
• Pregnant or breastfeeding women.

Full record on ClinicalTrials.gov

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