AK104 Alone or in Combination With Chemotherapy in the First-line Treatment of ESCC

NCT05522894 | Unknown Phase 2

• 1 other identifier: NCC3649
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a two-arm, open, multicenter clinical study to evaluate the efficacy and safety of AK104 alone or in combination with cisplatin and paclitaxel in the treatment of advanced esophageal squamous carcinoma without systemic therapy.

Conditions

Unresectable Esophageal Squamous Cell Carcinoma; Locally Advanced Esophageal Squamous Cell Carcinoma; Metastatic Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is proportion of subjects with complete response(CR) or partial response(PR), based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1.

  Up to approximately 2 years

Secondary Outcomes (5)

• Progression-free survival (PFS)

  Up to approximately 2 years

• Overall survival (OS)

  Up to approximately 2 years

• Disease control rate (DCR)

  Up to approximately 2 years

• Duration of response (DoR)

  Up to approximately 2 years

• Incidence and severity of adverse events(AEs)

  Up to approximately 2 years

Other Outcomes (2)

• The expression of PD-L1 in tumor tissue

  Up to approximately 2 years

• The level of ctDNA in blood

  Up to approximately 2 years

Study Arms (2)

Cohort A

EXPERIMENTAL

AK104 alone

Drug: AK104

Cohort B

EXPERIMENTAL

AK104 in combination with chemotherapy

Drug: AK104; Drug: Cisplatin; Drug: Paclitaxel

Interventions

AK104 DRUG

10mg/kg IV every 3 weeks (Q3W)

Also known as: Cadonilimab

Cohort A; Cohort B

Cisplatin DRUG

75mg/m2 IV every 3 weeks (Q3W)

Also known as: DDP

Cohort B

Paclitaxel DRUG

175mg/m2 IV every 3 weeks (Q3W)

Also known as: PTX

Cohort B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 to 75 years old, men or women are not limited
• Histologically or cytologically confirmed as esophageal squamous cell carcinoma (including the gastroesophageal junction), (adenosquamous carcinoma with a predominantly squamous component is allowed)
• Unresectable, locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma
• Patients who have never received systemic antitumor therapy
• ECOG score 0-1
• Patients who have measurable lesions that meet RECIST 1.1 criteria
• Patients who are expected to survive more than 3 months
• Women of childbearing age must have a negative pregnancy test (serum or urine) and voluntarily use an appropriate method of contraception
• Patients who are voluntarily enrolled in the study and sign an informed consent form (ICF)
• Patients who are well adherent and able to follow up the study protocol
• Patients with normal function organs, no serious abnormalities of blood, heart, lung, liver, kidney function, and immunodeficiency diseases.
• Patients with normal coagulation function, no active bleeding, and thrombotic disease
• cohort A: AK104 monotherapy cohort enrolling patients with esophageal cancer tumor tissue PD-L1 CPS ≥ 5 (uniformly using Dako 22C3 antibody)

You may not qualify if:

• Locally advanced esophageal cancer that can be radically resectable or potentially cured by radiotherapy
• Other malignancies diagnosed within 5 years prior to the first administration of the study drug, except effectively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or effectively resected in situ cervical and/or breast cancer
• Symptomatic central nervous system metastases (brain metastases confirmed stable by imaging for more than 3 months can be enrolled)
• A serious infection (CTCAE \> grade 2) such as severe pneumonia requiring hospitalization, bacteremia, or infectious comorbidities that occurred within 4 weeks prior to the first administration of the study drug; baseline chest imaging suggestive of active pulmonary inflammation with clinically relevant signs or symptoms; signs and symptoms of infection within 2 weeks prior to the first administration of study drug, or requiring oral, or intravenous antibiotic therapy. Excluding prophylactic use of antibiotics
• Patients with previous and current interstitial pneumonia, pneumoconiosis, drug-related pneumonia, or severely impaired lung function that may interfere with the detection and management of suspected drug-related pulmonary toxicity; patients with radiation pneumonia within 6 months
• Patients with active tuberculosis infection detected by history or CT examination, patients with a history of active tuberculosis infection within 1 year prior to enrollment, or patients with a history of active tuberculosis infection more than 1 year ago but without formal treatment
• Patients previously treated with immune checkpoint inhibitors
• Patients who have a congenital or acquired immune deficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive for hepatitis C antibodies and HCV-RNA above the lower limit of detection of the assay) or combined hepatitis B and hepatitis C co-infection
• Patients who have a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
• The presence of thrombosis-type diseases or using anticoagulant drugs
• Patients with any serious or uncontrolled systemic disease that, in the opinion of the investigator, may increase the risk associated with participation

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead
• Akeso Pharmaceuticals, Inc.: collaborator

Related Publications (1)

• Qu W, Gao J, Zhang B, Yang M, Wang Y, Liu Y, Guo Y, Guo S, Huang J. Cadonilimab combined with taxane and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma: an open-label, multicenter phase II trial. J Immunother Cancer. 2025 Oct 30;13(10):e012869. doi: 10.1136/jitc-2025-012869.

  PMID: 41167638 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Cisplatin; Paclitaxel

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jing Huang, M.D.

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yun Liu, M.D.

CONTACT

010-87788102; medliuyun@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: August 31, 2022
• Study Start: October 1, 2022
• Primary Completion: April 1, 2024
• Study Completion: October 1, 2024
• Last Updated: August 31, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share