A Prospective, Single-arm, Single-center, Exploratory Study of the Safety and Efficacy of Ivonescimab（AK112） Combined With Chemotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Rate of pathological complete response (PCR)
研究概览
简要总结
In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma patients was not significantly decreased. It is recommended that a treatment strategy be employed that integrates surgery with radiotherapy, chemotherapy, or immunotherapy, in order to enhance overall survival by improving local-regional tumor control and addressing microscopic metastases. Clinical research indicates that combining anti-PD-1/L1 and anti-VEGF antibodies enhances anti-tumor effects in esophageal squamous cell carcinoma. Ivonescimab, a humanized bispecific monoclonal antibody targeting PD-1/VEGF. This single-arm, prospective, exploratory study is planned to evaluate the combination of ivonescimab and chemotherapy in neoadjuvant therapy for resectable esophageal squamous cell carcinoma, with the aim of providing new therapeutic options for this condition.
详细描述
China with high incidence of esophageal cancer, the number of new cases and deaths account for about 50% of the world every year. In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma patients was not significantly decreased. For patients with locally advanced esophageal squamous cell carcinoma, direct surgery is not effective. It is difficult to achieve radical resection by surgery merely, and even if many patients receive surgery, they may eventually have tumor recurrence and poor survival rate.
It is recommended that a treatment strategy be employed that integrates surgery with radiotherapy, chemotherapy, or immunotherapy, in order to enhance overall survival by improving local-regional tumor control and addressing microscopic metastases. Consequently, the exploration of effective perioperative adjuvant or neoadjuvant treatment modalities aimed at reducing the risk of postoperative recurrence and enhancing postoperative survival rates is a critical focus in the treatment of esophageal squamous cell carcinoma.
Recently, PD-1/ PD-L1 immunocheckpoint inhibitor may become a new method for the treatment of esophageal cancer. Clinical research indicates that combining anti-PD-1/L1 and anti-VEGF antibodies enhances anti-tumor effects in esophageal squamous cell carcinoma. Ivonescimab, a humanized bispecific monoclonal antibody targeting PD-1/VEGF, boosts the immune system's anti-tumor response and inhibits VEGF's immunosuppressive effects, enhancing T cell infiltration in tumors. In patients with locally advanced esophageal cancer, the efficacy of ivonescimab combined with chemotherapy for sequential radical surgery is still unclear. Therefore, a single-arm, prospective, exploratory study is planned to evaluate the combination of ivonescimab and chemotherapy in neoadjuvant therapy for resectable esophageal squamous cell carcinoma, with the aim of providing new therapeutic options for this condition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •signed informed consent;
- •patients age 18 to 75 years old
- •primary resectable, histologically confirmed esophageal squamous cell cancer;
- •Esophageal squamous cell carcinoma the clinical stage was II-IVA (according to AJCC TNM stage, 8th edition).
- •No distant metastasis, the diseases could be resectable assessed by thoracic oncologist;
排除标准
- •with significant cardiovascular disease;
- •current treatment with anti-viral therapy or HBV;
- •Female patients who are pregnant or lactating;
- •history of malignancy within 5 years prior to screening;
- •active or history of autoimmune disease or immune deficiency;
- •signs of distant metastases.
研究组 & 干预措施
Ivonescimab（AK112） Combined With Chemotherapy
Preoperative neoadjuvant therapy for 3 cycles. Radical surgery is performed 4-8 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient.
Ivonescimab（AK112） can be maintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.
干预措施: Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy (Combination Product)
Ivonescimab（AK112） Combined With Chemotherapy
Preoperative neoadjuvant therapy for 3 cycles. Radical surgery is performed 4-8 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient.
Ivonescimab（AK112） can be maintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.
干预措施: Esophagectomy (Procedure)
Ivonescimab（AK112） Combined With Chemotherapy
Preoperative neoadjuvant therapy for 3 cycles. Radical surgery is performed 4-8 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient.
Ivonescimab（AK112） can be maintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.
干预措施: Sample (Other)
结局指标
主要结局
Rate of pathological complete response (PCR)
时间窗: 1 month after surgery
The proportion of the surgical population with PCR, which was defined no residual invasive tumor cells were found in the pathological examination of resected specimens, including the primary tumor and lymph nodes.
次要结局
- Incidence of Treatment-related Adverse Events(1 month after surgery)
- The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients(3 month after surgery)
- Rate of major pathological response (MPR)(1 month after surgery)
- Rate of objective response rate (ORR)(before surgery)
- Incidence of Treatment-related Adverse Events(1 month after surgery)
- 2-year and 5-year overall survival rate(2-year and 5-year after enrolled)
- The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients(3 month after surgery)