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

NCT ID: NCT06718543

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-10
• Study Completion Date: 2027-10-31

Brief Summary

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.

Detailed 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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SCRT followed by CapeOX regimen combined with AK112

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).

Group Type: EXPERIMENTAL

AK112 with SCRT and CapeOX

Intervention Type: DRUG

In the 1st week, neoadjuvant short-course radiotherapy will be administered (25 Gy in 5 fractions over 5 days). After a 7day 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).

SCRT followed by AK112

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).

Group Type: EXPERIMENTAL

AK112 with SCRT

Intervention Type: DRUG

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).

Interventions

AK112 with SCRT and CapeOX

In the 1st week, neoadjuvant short-course radiotherapy will be administered (25 Gy in 5 fractions over 5 days). After a 7day 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).

Intervention Type: DRUG

AK112 with SCRT

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).

Intervention Type: DRUG

Other Intervention Names

short-course radiotherapy; CapeOX

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

fan li

OTHER

Sponsor Role: lead

Responsible Party

fan li

Prof.

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Daping Hospital

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Fan LI, PhD

Role: CONTACT

levinecq@163.com

+8618696539200

Haode Shen, MD

Role: CONTACT

imshd@qq.com

+8617783437391

Facility Contacts

Fan Li, PhD

Role: primary

levinecq@163.com

+8618696539200

Haode Shen, MD

Role: backup

imshd@qq.com

+8617783437391

Other Identifiers

TRIUNITE-03

Identifier Type: -

Identifier Source: org_study_id