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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Cadonilimab (AK104); Drug: Cisplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wenting Li; Phone Number: 18116403289; Email: wenting01.li@akesobio.com

Study Locations

• China
  • Xi'an, China
    • Recruiting
    • The Second Affiliated Hospital of Air Force Medical University
    • Contact: Xiaolong Yan; Phone Number: 15991269383; Email: 47260934@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadonilimab (dose 1) combined with Cisplatin and Paclitaxel	Drug: Cadonilimab (AK104); Specified doses on specified days.; Drug: Cisplatin; IV infusion; 75mg/m2; Drug: Paclitaxel; IV infusion; 175mg/m2
Experimental: Cadonilimab (dose 2) combined with Cisplatin and Paclitaxel	Drug: Cadonilimab (AK104); Specified doses on specified days.; Drug: Cisplatin; IV infusion; 75mg/m2; Drug: Paclitaxel; IV infusion; 175mg/m2
Active Comparator: Cisplatin and Paclitaxel	Drug: Cisplatin; IV infusion; 75mg/m2; Drug: Paclitaxel; IV infusion; 175mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) rate as assessed by the investigator	Proportion of subjects with no tumor residue in the primary tumor and regional lymph nodes.	Up to approximately 2 years
Adverse Event (Phase II stage)	Incidence and severity of adverse events (AEs), rate of delayed surgery, and clinically significant abnormal laboratory findings.	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	Proportion of subjects with pathologically complete resection of primary tumors	Up to approximately 2 years
Major Pathological Response (MPR) rate as assessed by the investigator	Proportion of subjects with ≤10% residual live tumor cells as assessed by the investigator.	Up to approximately 2 years
Event Free Survival (EFS)	Time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause.	Up to approximately 5 years
Disease Free Survival (DFS)	Time from surgery to local or distant recurrence, or death due to any cause.	Up to approximately 5 years
Overall Survival (OS)	Time from randomization until death from any cause.	Up to approximately 5 years
Overall Response Rate (ORR)	Proportion of subjects with complete response (CR) or partial response (PR) during the neoadjuvant stage.	Up to approximately 2 years
Disease Control Rate (DCR)	Evaluation of DCR based on RECIST v1.1	Up to approximately 2 years
Pharmacokinetics (PK)	PK parameters: serum concentrations of Cadonilimab at different point of time	Up to approximately 2 years
Anti-Drug Antibodies(ADAs)	Proportion of subjects with detectable ADA.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Xiaolong Yan, The Second Affiliated Hospital of Air Force Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2025
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Estimated): December 4, 2025

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Paclitaxel; Cisplatin
• Other Study ID Numbers: AK104-312

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No