Perioperative cadonilimab plus neoadjuvant chemotherapy for resectable thoracic esophageal squamous cell carcinoma

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 trial will test whether adding cadonilimab to pre-surgery cisplatin/paclitaxel chemotherapy helps people with resectable esophageal squamous cell carcinoma have better outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: Cadonilimab, chemotherapy
• Locations: 1 site (Xi'an)
• Trial ID: NCT07263919 on ClinicalTrials.gov

What this trial studies

This randomized, controlled phase II/III multicenter trial compares perioperative cadonilimab combined with standard neoadjuvant cisplatin and paclitaxel chemotherapy versus neoadjuvant chemotherapy alone in adults with resectable locally advanced thoracic ESCC. Eligible patients (age 18–75, ECOG 0–1) must provide tumor tissue and have adequate organ and pulmonary function. Participants receive preoperative therapy followed by planned surgical resection, with monitoring for safety and efficacy endpoints such as pathological response and survival outcomes. The study is sponsored by Akeso and conducted at participating hospitals including The Second Affiliated Hospital of Air Force Medical University in Xi'an.

Who should consider this trial

Good fit: Adults 18–75 with pathologically confirmed resectable locally advanced thoracic ESCC, ECOG 0–1, adequate organ and pulmonary function, and available tumor tissue are ideal candidates.

Not a fit: Patients with distant metastases, unresectable disease, non-squamous histology, poor performance status, or prior surgeries that prevent standard reconstruction are unlikely to benefit.

Why it matters

Potential benefit: If successful, adding cadonilimab could increase preoperative tumor response and lower recurrence risk, potentially improving survival.

How similar studies have performed: Other trials combining immune checkpoint inhibitors with neoadjuvant chemotherapy in esophageal cancer have shown encouraging pathological responses, although cadonilimab as a newer bispecific agent has more limited prior data.

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.

Where this trial is running

Xi'an

• The Second Affiliated Hospital of Air Force Medical University — Xi'an, China (Recruiting)

Study contacts

• Principal investigator: Xiaolong Yan — The Second Affiliated Hospital of Air Force Military Medical University
• Study coordinator: Wenting Li

Conditions Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma