CAPOX plus PD-1 antibody (toripalimab) with or without short-course radiotherapy for MSS locally advanced rectal cancer

A Prospective Randomized Phase II Trial of CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for Microsatellite Stable Locally Advanced Rectal Cancer (TORCH-iTNT)

This trial will try toripalimab combined with CAPOX chemotherapy, with or without a short course of radiotherapy, to see if it increases complete response rates in adults with MSS locally advanced rectal cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 192 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Toripalimab
• Locations: 1 site (Shanghai)
• Trial ID: NCT06281405 on ClinicalTrials.gov

What this trial studies

TORCH-iTNT is a randomized, phase II trial enrolling about 198 patients with locally advanced, MSS/pMMR rectal adenocarcinoma. Participants are assigned 1:1 to receive six cycles of toripalimab plus CAPOX chemotherapy (ToriCAPOX) with or without preceding short-course radiotherapy (25 Gy in 5 fractions). After total neoadjuvant therapy (TNT), patients proceed to total mesorectal excision (TME) or may enter a watch-and-wait pathway if they achieve a clinical complete response (cCR). The primary endpoint is the overall complete response rate (pathological pCR plus cCR), and secondary endpoints include high-grade acute adverse events, organ/anal preservation rate, and 3-year disease-free survival.

Who should consider this trial

Good fit: Adults 18–70 years old with histologically confirmed MSS/pMMR locally advanced rectal adenocarcinoma (cT3–T4 and/or node-positive), tumor ≤10 cm from the anal verge, good performance status, and no prior anti‑cancer therapy are the intended candidates.

Not a fit: Patients with metastatic disease, MSI‑high/dMMR tumors, prior radiotherapy/chemotherapy/immunotherapy, poor performance status, pregnancy, or recent other malignancies are unlikely to benefit or are ineligible.

Why it matters

Potential benefit: If successful, this approach could raise complete response rates and increase the chance of organ preservation for patients with MSS locally advanced rectal cancer.

How similar studies have performed: Some early trials combining chemotherapy, radiotherapy, and PD‑1 inhibitors have reported promising increases in response rates, but benefit in MSS rectal cancer remains experimental and not yet established.

Eligibility criteria

Inclusion Criteria

1. Age 18-70 years old, female and male;
2. Pathological confirmed adenocarcinoma;
3. The distance from anal verge ≤ 10 cm;
4. MSI/MMR status: MSS/pMMR;
5. Clinical stage T3-4 and/or N+, without distance metastases;
6. At least one of the following factors is present: distance from the anus ≤5 cm, cT4, cN2, positive cMRF, positive cEMVI, or positive lateral lymph nodes;
7. KPS ≥ 70;
8. No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
9. Baseline blood and biochemical indicators meet the following criteria: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST ≤ 2.5 ULN, Cr ≤ 1 ULN;
10. With good compliance and signed the consent form.

Exclusion Criteria

1. Pregnancy or breast-feeding women;
2. Known history of other malignancies within 5 years;
3. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
4. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
5. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
6. Uncontrolled infection which needs systemic therapy;
7. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
8. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
9. Allergic to any component of the therapy.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Zhen Zhang, MD — Fudan University
• Study coordinator: Zhen Zhang, MD

Conditions Locally Advanced Rectal Cancer; Neoadjuvant Therapy