Efficacy and Safety of Anlotinib Combined With Bemocizumab for Neoadjuvant Therapy of Esophageal Squamous Cell Carcinoma(ESCC)

Clinical Trial on the Efficacy and Safety of Anlotinib Combined With Bemocizumab for Neoadjuvant Therapy of Resectable Esophageal Squamous Cell Carcinoma

This study aims to explore the efficacy and safety of anlotinib combined with bemocizumab as neoadjuvant therapy for resectable esophageal squamous cell carcinoma, with the goal of improving the pathological complete response (pCR) rate and margin-negative resection(R0) resection rate in patients undergoing esophageal cancer surgery, as well as enhancing disease-free survival (DFS) in postoperative patients. This will provide guidance and new options for the treatment of patients with locally advanced esophageal cancer.

This is a prospective, single-arm, single-center clinical study aimed at evaluating the efficacy and safety of anlotinib combined with bemarituzumab in neoadjuvant treatment for resectable esophageal squamous cell carcinoma, with the goal of improving the pathological complete response (pCR) rate and margin-negative resection(R0) resection rate in patients undergoing esophageal cancer surgery, as well as enhancing disease-free survival (DFS) in postoperative patients.

The study plans to enroll 25 eligible participants who meet the inclusion and exclusion criteria. Patients will receive 3-4 cycles of neoadjuvant therapy prior to surgery, consisting of bemarituzumab at 1200 mg every 3 weeks and anlotinib at 8 mg daily from day 1 to day 14. 。 Surgical eligibility will be assessed 4-6 weeks after completion of neoadjuvant therapy. Patients achieving complete response (CR), partial response (PR), or stable disease (SD) will undergo surgery. Patients with progressive disease (PD) who are deemed operable by the investigator will also proceed to surgery; otherwise, they will be withdrawn from the study. The surgical approach will typically involve a standard three-incision thoracoabdominal laparoscopic esophagectomy, although Ivor-Lewis or Sweet procedures may also be used as appropriate. Postoperative adjuvant therapy will be administered based on individual patient conditions.

Following surgery, pathological evaluation will be performed to determine the primary endpoint, pathologic complete response (pCR). Subsequent follow-up will continue for 5 years to assess other secondary endpoints.

Inclusion Criteria:

1. Aged 18-70, both male and female
2. After gastroscopy/ultrasonic gastroscopy biopsy, the pathology suggests squamous cell carcinoma of the esophagus, and the clinical diagnosis is cT2N1-2M0 or cT3N0-2M0, with TNM staging of II-III B
3. Patients with non-cervical esophageal cance
4. The patient has not previously received systemic or local treatment for esophageal cancer, and according to the RECIST 1.1 criteria, there is at least one measurable lesion for imaging evaluation of neoadjuvant therapy
5. ECOG PS: 0-1
6. Expected survival duration ≥ 12 months
7. The subjects had no functional disorders of major organs, and the researchers assessed that thyroid, lung, liver, kidney, and heart functions were basically normal;
8. Women of childbearing age must have already taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days prior to enrollment, with a negative result, and be willing to use appropriate contraception during the trial and for 8 weeks after the last administration of the trial medication. For males, they must agree to use appropriate contraception during the trial and for 8 weeks after the last administration of the trial medication, or have undergone surgical sterilization
9. The subjects voluntarily joined this study, signed the informed consent form, exhibited good compliance, actively cooperated with the planned schedule by returning to the hospital for regular clinical follow-ups and necessary treatments, and cooperated with the regular collection of blood and tissue samples

Exclusion Criteria:

1. Within the past 5 years, there has been or is currently a co-occurrence of other malignant tumors, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invades the basement membrane)]
2. Patients with ulcerative esophageal squamous cell carcinoma
3. Patients with esophageal fistula or tracheal fistula;
4. Those who are allergic to anlotinib and bemusuban
5. Those with a history of immune deficiency, including HIV-positive or suffering from other acquired or congenital immune deficiency diseases, or those who have undergone organ transplantation
6. Patients with any severe and/or uncontrolled diseases
7. Unresolved toxic reactions above CTC AE Grade 1 caused by any previous treatment, excluding alopecia;
8. Individuals with multiple factors affecting oral medication administration, such as inability to swallow, chronic diarrhea, and intestinal obstruction
9. Urine routine test indicates proteinuria ≥++ and confirmed 24-hour urine protein quantitation > 1.0 g
10. Subjects who underwent major surgical procedures, incisional biopsies, or significant traumatic injuries within 28 days prior to grouping
11. Abnormal coagulation function: INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulant therapy; patients who have experienced any bleeding or hemorrhagic events ≥ CTCAE Grade 3 within 4 weeks before grouping, have unhealed wounds, ulcers, or fractures
12. Those who have experienced arterial or venous thromboembolic events within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism
13. Pregnant or lactating women
14. Patients with distant metastasis
15. Patients with significant bone marrow suppression
16. Suffering from mental illness or having a history of abuse of psychotropic drugs;
17. Patients who have participated in other drug clinical trials within 4 weeks;
18. Patients with concomitant diseases that, according to the researcher's judgment, pose serious risks to patient safety or affect patients' ability to complete the study
19. Individuals with hereditary bleeding tendency, coagulation dysfunction, potential invasion of large blood vessels, and other bleeding risks, who have experienced clinically significant bleeding symptoms or have a clear tendency to bleed within the previous 3 months before enrollment, such as gastrointestinal bleeding, bleeding gastric ulcer, and baseline fecal occult blood test result of ++ or above
20. Researchers consider those who are not suitable for inclusion