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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Complete Response Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent.
- •Age 18-80 years, male or female.
- •Histologically confirmed rectal adenocarcinoma.
- •Clinical baseline stage T3-4NxM0 or TxN1-2M0 by MRI assessment.
- •Able to swallow tablets.
- •ECOG Performance Status of 0-
- •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
排除标准
- •Allergy to monoclonal antibodies, AK112 components, or CapeOX regimen.
- •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.
研究组 & 干预措施
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).
干预措施: AK112 with SCRT and CapeOX (Drug)
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).
干预措施: AK112 with SCRT (Drug)
结局指标
主要结局
Complete Response Rate
时间窗: 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).
次要结局
- Adverse Events (AEs)(From baseline to 90 days after the last treatment dose.)
- Major Pathological Response (MPR)(At the time of surgery (approximately 12 weeks after treatment initiation).)
- Objective Response Rate (ORR)(Approximately 12 weeks after treatment initiation.)
- Progression-Free Survival (PFS)(Up to 36 months post-randomization.)
- Overall Survival (OS)(Up to 36 months post-randomization.)
- Organ Preservation Rate (OPR)(Approximately 12 months post-treatment initiation.)
- Tumor Response Based on RECIST 1.1(Approximately 12 weeks after treatment initiation.)
- Clinical Complete Response Rate (cCR)(Approximately 12 weeks after treatment initiation.)
- Pathological Complete Response (pCR)(Approximately 12 weeks after treatment initiation.)
研究者
fan li
Prof.
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University