Perioperative Cadonilimab Combined With Neoadjuvant Chemotherapy in Resectable Esophageal Squamous Cell Carcinoma (ESCC)

Official title

A Randomized, Controlled, Multi-center Phase II/III Clinical Trial of Perioperative Cadonilimab Combined With Neoadjuvant Chemotherapy in Patients With Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma (ESCC)

Overview

This is a randomized, controlled, multi-center phase II/III study. All patients are resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of perioperative Cadonilimab combined with neoadjuvant chemotherapy versus neoadjuvant chemotherapy in patients with resectable ESCC.

Interventions

• Drug Cadonilimab (AK104)
  Specified doses on specified days.
• Drug Cisplatin
  IV infusion; 75mg/m2
• Drug Paclitaxel
  IV infusion; 175mg/m2

Primary outcome measures

• Pathologic Complete Response (pCR) rate as assessed by the investigator [Time frame: Up to approximately 2 years]
• Adverse Event (Phase II stage) [Time frame: Up to approximately 5 years]

Secondary outcome measures (9)

• Major Pathological Response (MPR) rate as assessed by the investigator [Time frame: Up to approximately 2 years]
• R0 resection rate [Time frame: Up to approximately 2 years]
• Event Free Survival (EFS) [Time frame: Up to approximately 5 years]
• Disease Free Survival (DFS) [Time frame: Up to approximately 5 years]
• Overall Survival (OS) [Time frame: Up to approximately 5 years]
• Overall Response Rate (ORR) [Time frame: Up to approximately 2 years]
• Disease Control Rate (DCR) [Time frame: Up to approximately 2 years]
• Pharmacokinetics (PK) [Time frame: Up to approximately 2 years]
• Anti-Drug Antibodies(ADAs) [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
• ≥18 years old and ≤ 75 years (regardless of sex).
• Pathologically confirmed esophageal squamous cell carcinoma, assessed as resectable.
• Adequate pulmonary function.
• Adequate tumor tissue samples.
• ECOG performance status of 0-1.
• Adequate organ function.
• Within 7 days prior to the first dose, women of childbearing potential must have a negative urine or serum pregnancy test and agree to use effective contraception during the study treatment period and for 120 days after the last dose.

Exclusion criteria

• Presence of suspected distant metastatic lesions, or locally advanced unresectable disease.
• Histologically confirmed as other pathological types.
• Previous surgery precludes the use of gastric substitution for esophageal reconstruction in the current procedure.
• History of other malignant tumors within the past 5 years.
• Within 4 weeks prior to randomization, presence of conditions such as severe esophagogastric varices, active ulcers, unhealed wounds, gastrointestinal perforation, or intestinal obstruction.
• Active or documented history of inflammatory bowel disease.
• Clinically symptomatic or recurrent pleural, pericardial, or ascitic fluid requiring drainage.
• Uncontrolled concurrent illnesses.
• Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks prior to randomization.
• History of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment.
• History of severe bleeding tendency or coagulation dysfunction.
• Arterial thromboembolic events within 6 months prior to randomization.
• History or current presence of non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoids.
• Known psychiatric disorders, drug abuse, or substance addiction.
• Pregnant or lactating women.
• Prior systemic or local antitumor therapy for locally advanced esophageal squamous cell carcinoma.
• Systemic non-specific immunomodulatory therapy within 2 weeks prior to randomization.
• Major surgery or severe trauma within 4 weeks prior to randomization.
• Known allergy to any component of the investigational drug(s).
• Active autoimmune disease requiring systemic treatment within 2 years prior to randomization.
• Active hepatitis B infection.
• Known active tuberculosis.
• Severe infections within 4 weeks prior to randomization.
• History of immunodeficiency or positive HIV test.
• Known active syphilis infection.
• Live vaccination within 4 weeks prior to randomization or planned during the study.
• History of allogeneic organ transplantation or hematopoietic stem cell transplantation.
• Is currently participating in a study of an investigational agent or using an investigational device.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Air Force Medical University — Xi'an

Identifiers

NCT: NCT07263919 · AK104-312

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗