Short-course Radiotherapy Based TNT Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer

A Prospective Phase II Trial of Short-course Radiotherapy Based Total Neoadjuvant Therapy Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer (TORCH）

TORCH is a prospective, multicentre, randomized phase II trial. 130 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B. Group A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives 2 cycles of ToriCAPOX followed by SCRT and 4 cycles of ToriCAPOX. TME surgery is scheduled after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, etc.

Inclusion Criteria:

1. Pathological confrmed adenocarcinoma
2. Clinical stage T3-4 and/or N+
3. The distance from anal verge ≤12 cm
4. Without distance metastases
5. Age 18-70 years old, female and male
6. KPS > =70
7. 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
8. 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 previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc
4. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy)
5. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction
6. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment
7. Uncontrolled infection which needs systemic therapy
8. Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
9. Known history of human immunodefciency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
10. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (i.e., HBsAg positive or HBV DNA positive, HCV RNA positive if anti-HCV antibody testing positive)
11. Allergic to any component of the therapy