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

Phase 2

Recruiting

• Conditions: Rectal Cancer
• Interventions: Drug: AK112 with SCRT and CapeOX; Drug: AK112 with SCRT

• Registration Number: NCT06718543
• Lead Sponsor: fan li

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.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-02
• Study First Submitted QC: 2024-12-02
• Study First Posted: 2024-12-05
• Study Start: 2025-02-10
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-10
• Primary Completion: 2026-10-31
• Study Completion: 2027-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SCRT followed by CapeOX regimen combined with AK112	AK112 with SCRT and CapeOX	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).
SCRT followed by AK112	AK112 with SCRT	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).

Primary Outcome Measures

Name	Time	Method
Complete Response Rate	From treatment initiation to post-neoadjuvant therapy evaluation (approximately 12 weeks).	Proportion of patients achieving either a pathological complete response (pCR) or a clinical complete response (cCR).

Secondary Outcome Measures

Name	Time	Method
Adverse Events (AEs)	From baseline to 90 days after the last treatment dose.	Incidence, type, and severity of adverse events graded according to CTCAE v5.0, including their correlation with the study drug.
Major Pathological Response (MPR)	At the time of surgery (approximately 12 weeks after treatment initiation).	Proportion of patients with ≤10% residual viable tumor cells in resected specimens.
Objective Response Rate (ORR)	Approximately 12 weeks after treatment initiation.	Proportion of patients with complete response (CR) or partial response (PR) based on radiological assessments using RECIST 1.1 criteria.
Progression-Free Survival (PFS)	Up to 36 months post-randomization.	Time from randomization to disease progression or death from any cause.
Overall Survival (OS)	Up to 36 months post-randomization.	Time from randomization to death from any cause.
Organ Preservation Rate (OPR)	Approximately 12 months post-treatment initiation.	Proportion of patients avoiding major surgery while retaining organ functionality.
Tumor Response Based on RECIST 1.1	Approximately 12 weeks after treatment initiation.	Evaluation of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) using RECIST 1.1 criteria.
Clinical Complete Response Rate (cCR)	Approximately 12 weeks after treatment initiation.	Proportion of patients achieving clinical complete response based on clinical examination and imaging assessments.
Pathological Complete Response (pCR)	Approximately 12 weeks after treatment initiation.	Absence of tumor cells in the primary tumor and regional lymph nodes in surgical specimens.

Trial Locations

Locations (1)

Daping Hospital; 🇨🇳 Chongqing, Chongqing, China