602TiP - Radical concurrent chemoradiotherapy with DDP/5-FU and PD-1 antibody for non-metastatic rectal squamous cell carcinoma: A multicenter, prospective, single-arm, phase II study

Background

Rectal squamous cell carcinoma (RSCC) is a rare subtype, accounting for up to 0.3% of all rectal cancers. Due to its rarity, clinical guidelines for staging and treatment are lacking, necessitating further exploration. The emergence of immunotherapy, such as programmed cell death protein 1 (PD-1) antibodies, presents a novel strategy for RSCC, potentially enhancing the efficacy of CRT through synergistic effects. Combining CRT with PD-1 may bolster immunogenicity by inducing cell death, antigen release, and immune-mediated tumor surveillance, thus improving anti-tumor activity. This study aims to assess the safety and efficacy of CRT combined with PD-1 immunotherapy (CRT-I) in RSCC patients.

Trial design

This is a multicenter, prospective, single-arm, Phase II clinical study designed to provide evidence-based support for PD-1 monoclonal antibody treatment in combination with CRT, aiming to enhance the prognosis of RSCC patients. Specifically, it is the first prospective study to evaluate whether PD-1, in combination with radical CRT, improves survival in RSCC patients based on complete response rate (CRR), survival outcomes, toxicity, and quality of life. Eligible patients will receive DDP/5-FU chemotherapy (DDP 75 mg/m2, d1, intravenous infusion; 5-FU 1000 mg/m2, d1-4, continuous intravenous infusion; q4w for 4 cycles) and long-course intensity-modulated radiation therapy (IMRT) combined with PD-1 monoclonal antibody (Sintilimab, 200mg/dose, q4w for 4 cycles). IMRT will commence in the third week following the first chemotherapy cycle, delivering a total dose of 50-54 Gy in 2 Gy fractions. Key inclusion criteria encompass age 18 to 75, pathologically confirmed RSCC, absence of distant metastases. Main exclusion criteria include distant metastases, long-term immunosuppressive drug use. The primary endpoint is 3-year disease-free survival (DFS), with secondary endpoints including 3-year overall survival (OS), relapse-free survival (RFS), metastasis-free survival (DMFS). A total of 20 patients are planned for enrollment, with 2 patients enrolled as of May 5th, 2024.

Clinical trial identification

NCT06364384.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.