Neoadjuvant Short-Course Radiotherapy With or Without Chemotherapy and AK112 in Locally Advanced Rectal Cancer (TRIUNITE-03)

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Status and phase: Enrolling; Phase 2

Conditions: Rectal Cancer

Treatments: Drug: AK112 with SCRT; Drug: AK112 with SCRT and CapeOX

Study type: Interventional

Funder types: Other

Identifiers

NCT06718543

TRIUNITE-03

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

SCRT followed by CapeOX regimen combined with AK112

Experimental group

Description:

Patients will receive short-course radiotherapy (SCRT) followed by chemotherapy (CapeOX regimen) combined with AK112: In the 1st week, neoadjuvant short-course radiotherapy will be administered (25 Gy in 5 fractions over 5 days). After a 7-day interval, patients will receive 2 cycles of CapeOX chemotherapy combined with AK112 (every 3 weeks; Day 1: Oxaliplatin, 130 mg/m², IV infusion; Day 1: AK112, 20 mg/kg, IV infusion; Day 1 to Day 14: Capecitabine, 850-1000 mg/m², BID, orally).

Treatment:

Drug: AK112 with SCRT and CapeOX

SCRT followed by AK112

Experimental group

Description:

Patients will receive short-course radiotherapy (SCRT) followed by AK112: In the 1st week, neoadjuvant short-course radiotherapy will be administered (25 Gy in 5 fractions over 5 days). After a 7-day interval, patients will receive 2 cycles of AK112 treatment (Day 1: AK112, 20 mg/kg, IV infusion).

Treatment:

Drug: AK112 with SCRT