Neoadjuvant Cadonilimab Combined With Anlotinib in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

NCT06426797 | Not Yet Recruiting Phase 2

• 1 other identifier: AK104-IIT-C-N1-0104
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if cadonilimab combined with anlotinib can be a safe and effective neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). The main questions it aims to answer are: What level of pathological complete response (pCR) rate can be achieved with this neoadjuvant regimen? Is this neoadjuvant regimen safe enough with acceptable toxicity? Participants will: Receive cadonilimab (10mg/Kg, ivgtt, d1) and anlotinib (12mg, P.O., d1-d14) on a 21-day regimen for 3 cycles. Undertake radical resection of ESCC after neoadjuvant therapy if there is no surgical contraindication. Accept an follow-up for 2 years after surgery.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma

Keywords

esophageal squamous cell carcinoma; neoadjuvant immunotherapy; pathological complete response

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  Pathological complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in primary tumor site or lymph nodes as evaluated by blinded independent pathological review (BIPR).

  Within 1 week after surgery

Secondary Outcomes (4)

• Major Pathological Response (MPR) Rate

  Within 1 week after surgery

• Objective Response Rate (ORR)

  Within 1 week before surgery

• Treatment Emergent Adverse Events (TEAE)

  Up to 24 months after participation

• Event-free Survival (EFS)

  Up to 24 months after participation

Study Arms (1)

locally advanced ESCC

EXPERIMENTAL

Patients with locally advanced esophageal squamous cell carcinoma

Drug: Cadonilimab plus anlotinib

Interventions

Cadonilimab plus anlotinib DRUG

cadonilimab (10mg/Kg, ivgtt, d1) and anlotinib (12mg, P.O., d1-d14) on a 21-day regimen for 3 cycles

locally advanced ESCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent and understand and agree to comply with the requirements of this study as well as the assessment schedule.
• Be at least 18 years of age on the date of signing the ICF.
• Histopathologically confirmed esophageal squamous cell carcinoma: the clinical stage is T1-2N1-3M0, T2 (diameter≥3 cm) N0M0 or T3-4aN0-3M0 (stage II-IVA), and the staging should be based on the AJCC 8th edition esophageal cancer staging system.
• Patients are asked to provide an archival tumor tissue sample (FFPE tissue block or approximately 15 \[≥6\] freshly cut unstained FFPE sections) and a pathology report of this baseline sample. If no archival sample is available or the sample is not available, a biopsy sample is requested at baseline.
• Prior to study enrollment, patients are evaluated by thoracic surgeon in charge of surgery to verify that they meet the study requirements for R0 resection with radical curative intent.
• Cardiac and pulmonary function is good, and surgical resection for curative purposes is confirmed, and cardiopulmonary function tests and respiratory or cardiology consultation can be completed if necessary.
• Measurable disease as assessed by the investigator according to RECIST version 1.1.
• Eligible for anlotinib treatment.
• ECOG performance status ≤ 2 points.
• ≤ 14 days prior to enrollment, the following laboratory test values during the screening period suggest that the patient has good organ function:
• Patient has not had a blood transfusion or use of growth factor supportive therapy within ≤14 days prior to blood draw, when the following items are tested prior to enrollment:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet ≥ 75×109/L
• Hemoglobin ≥ 90 g/L
• Glomerular filtration rate (GFR) estimated by the Cooperative Equation for Epidemiology of Chronic Kidney Disease ≥45mL/min/1.73 m2.

You may not qualify if:

• Previous treatment for current esophageal cancer, including chemotherapy or radiotherapy.
• Prior receipt of antibodies or drugs targeting immune checkpoint pathways, including but not limited to anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4), anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• Patients with non-squamous cell carcinoma.
• Presence of locally advanced, unresectable disease, regardless of disease stage and presence or absence of metastases (stage IV).
• Active autoimmune disease or history of autoimmune disease that may recur.
• Note: Patients with the following conditions do not need to be excluded and can proceed for further enrollment screening:
• Well-controlled type I diabetes
• Hypothyroidism (as long as it is treated with hormone replacement therapy alone)
• Well-controlled celiac disease
• Skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia)
• Any other illness that is not expected to recur in the absence of an external trigger
• Any active malignancy in the ≤ 2 years prior to enrollment, with the exception of the specific cancers studied in this study and cancers that have recured locally after radical therapy (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ).
• Any condition requiring systemic treatment with corticosteroids (prednisone or equivalent\> 10 mg/day) or other immunosuppressive medications within ≤14 days prior to enrollment.
• Note: Patients with current or prior use of any of the following steroid regimens do not need to be excluded:
• Adrenal replacement steroids (prednisone or equivalent\> 10 mg/day)

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Akeso Pharmaceuticals, Inc.: collaborator

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Fan Yang, M.D.

  Peking University People's Hospital

  STUDY CHAIR

Central Study Contacts

Fan Yang, M.D.

CONTACT

+86-010-88326657; yangfan@pkuph.edu.cn

Xiang Yan, M.D.

CONTACT

+86-13581786750; yxiang301@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Thoracic Surgery

Model Details: Patients with locally advanced resectable esophageal squamous cell carcinoma

Study Record Dates

• First Submitted: May 19, 2024
• First Posted: May 23, 2024
• Study Start: May 1, 2024
• Primary Completion: May 1, 2025
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share