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.
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).
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;
Single group
Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy
Combination productIvonescimab（AK112) 20mg/kg, IV, Day 1; Albumin paclitaxel 260mg/m2, Day 1; carboplatin AUC=5, Day 1; Preoperative neoadjuvant therapy for 3 cycles, one cycle every 21 days.
Esophagectomy
Procedure/SurgeryPrior to each surgical procedure, the department engaged in comprehensive discussions and deliberations to ascertain and establish the most suitable course of action. Minimally invasive Ivor-Lewis (intrathoracic anastomosis) or McKeown (neck anastomosis) esophagectomy, including two field extensive lymphadenectomies, was performed according to the tumor location. The resection length should be at least 5cm from the tumor origin according to prechemotherapy by endoscopy. The surgeries will be performed by surgeons with rich experience. Minimally invasive esophagectomy, can be performed using the da Vinci surgical robot, thoracoscope, or laparoscope, or by using an open approach, as judged appropriate by the surgeon.
Sample
Other interventionBlood, Tumour will be Collected from participant. Fate of sample is Destruction after use. 5 ml of peripheral blood was collected the day before each of the immunotherapy sessions and after surgery. Tumour sample will be collected before neoadjuvant therapy and during surgery.
Rate of pathological complete response (PCR)
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.
Rate of major pathological response (MPR)
The proportion of the surgical population with MPR, which was defined in the pathological examination of resected specimens, the proportion of residual tumor cells was less than 10%.
Rate of objective response rate (ORR)
The proportion of subjects with imaging PR or CR assessed according to RECIST 1.1 criteria
2-year and 5-year overall survival rate
The proportion of all study cases in which no death from any cause occurred within 2 years and 5 years after surgery
Incidence of Treatment-related Adverse Events
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
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