Neoadjuvant Short-Course Radiotherapy With or Without Chemotherapy and AK112 in Locally Advanced Rectal Cancer

A Multicenter, Randomized, Parallel, Non-Controlled, Prospective Phase II Study of Neoadjuvant Short-Course Radiotherapy Sequential With AK112 With or Without Chemotherapy for Locally Advanced Rectal Cancer

This phase II multicenter, randomized study evaluates the safety and efficacy of neoadjuvant short-course radiotherapy (SCRT) sequentially combined with AK112 (Envafolimab) with or without chemotherapy in patients with locally advanced rectal cancer (LARC). The study also aims to identify biomarkers predicting tumor response and develop efficacy prediction models.

The study is designed as a two-arm, randomized, open-label, prospective trial. Patients with locally advanced rectal adenocarcinoma will be randomly assigned to one of two treatment groups:

Arm A: SCRT followed by chemotherapy (CapeOX) combined with AK112. Arm B: SCRT followed by AK112 alone. Primary and secondary outcome measures include complete response rate (CR), safety, pathological and radiological response rates, and biomarkers associated with treatment response. The trial will enroll 100 participants across multiple centers over three years.

Inclusion Criteria:

1. Signed written informed consent.
2. Age 18-80 years, male or female.
3. Histologically confirmed rectal adenocarcinoma.
4. Clinical baseline stage T3-4NxM0 or TxN1-2M0 by MRI assessment.
5. Able to swallow tablets.
6. ECOG Performance Status of 0-1.
7. No prior treatment for rectal cancer, including surgery, radiotherapy, 8.chemotherapy, immunotherapy, or targeted therapy.

9.Fit for surgery with no contraindications. 10.Normal organ function. 11.Tumor ≤12 cm from the anal verge

Exclusion Criteria:

1. Allergy to monoclonal antibodies, AK112 components, or CapeOX regimen.
2. Previous or current use of immune checkpoint inhibitors or immune-related 3.treatments.

4.Active autoimmune diseases or history of significant autoimmune conditions. 5.Immunodeficiency disorders or history of organ/bone marrow transplantation. 6.Uncontrolled cardiovascular conditions (e.g., heart failure, unstable angina, recent MI).

7.Severe infection within 4 weeks or active pulmonary infections. 8.Active hepatitis B or C infection. 9.Diagnosis of other malignancies within 5 years (except low-risk cancers). 10.Pregnant or breastfeeding women.