- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05522894
AK104 Alone or in Combination With Chemotherapy in the First-line Treatment of ESCC
August 28, 2022 updated by: Jing Huang, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
A Multicenter, Phase II Clinical Study of AK104 (Anti-PD-1/CTLA-4 Bispecific Antibody) Alone or in Combination With Chemotherapy in the First-line Treatment of Advanced Esophageal Squamous Cell Carcinoma
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.
Study Overview
Status
Not yet recruiting
Conditions
Intervention / Treatment
Detailed Description
During the treatment, eligible patients in cohort A with PD-L1 CPS ≥5 will receive AK104 10 mg/kg, intravenously, every 3 weeks (maximum 24 months of dosing); in cohort B, regardless of PD-L1 expression, eligible patients will receive AK104 10 mg/kg, intravenously, every 3 weeks (maximum 24 months of dosing), in combination with cisplatin (75 mg/m2) and paclitaxel (175 mg/m2), Q3W (up to 6 cycles, the specific cycles will be determined by the investigator).
Thereafter, AK104 maintenance therapy will be continued until disease progression, intolerable toxicity, withdrawal of informed consent, death, or end of the study, whichever occurred first (maximum duration of treatment with AK104 should be less than 12 months).
When patients with initially unresectable disease transformed into resectable, an operation can be considered and the original regimen may be used after surgery.
Study Type
Interventional
Enrollment (Anticipated)
80
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Yun Liu, M.D.
- Phone Number: 010-87788102
- Email: medliuyun@163.com
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 73 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A
AK104 alone
|
10mg/kg IV every 3 weeks (Q3W)
Other Names:
|
Experimental: Cohort B
AK104 in combination with chemotherapy
|
10mg/kg IV every 3 weeks (Q3W)
Other Names:
75mg/m2 IV every 3 weeks (Q3W)
Other Names:
175mg/m2 IV every 3 weeks (Q3W)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: Up to approximately 2 years
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: Up to approximately 2 years
|
Progression-free survival (PFS) is defined as the time from the first dose of investigational products until documentation of PD (as per RECIST v1.1) or death due to any cause, whichever occurs first.
|
Up to approximately 2 years
|
Overall survival (OS)
Time Frame: Up to approximately 2 years
|
Overall survival (OS) is defined as the time from the first dose of investigational products until death due to any cause.
|
Up to approximately 2 years
|
Disease control rate (DCR)
Time Frame: Up to approximately 2 years
|
Disease control rate (DCR) is defined as the proportion of subjects achieving a best of response(BOR) of confirmed CR and PR and stable disease(SD) per RECIST v1.1.
|
Up to approximately 2 years
|
Duration of response (DoR)
Time Frame: Up to approximately 2 years
|
Duration of response (DoR) is defined as the period from the first documentation of confirmed response (CR or PR) to the first documentation of progressive disease(PD) (as per RECIST v1.1) or death due to any cause, whichever occurs first.
|
Up to approximately 2 years
|
Incidence and severity of adverse events(AEs)
Time Frame: Up to approximately 2 years
|
Incidence and severity of AEs is aim to evaluate the safety of AK104 alone or combination with chemotherapy.
|
Up to approximately 2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The expression of PD-L1 in tumor tissue
Time Frame: Up to approximately 2 years
|
The expression of PD-L1 is aim to investigate the relationship between PD-L1 and anti-tumor efficacy.
|
Up to approximately 2 years
|
The level of ctDNA in blood
Time Frame: Up to approximately 2 years
|
The level of ctDNA is aim to investigate the relationship between ctDNA and anti-tumor efficacy.
|
Up to approximately 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Jing Huang, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
October 1, 2022
Primary Completion (Anticipated)
April 1, 2024
Study Completion (Anticipated)
October 1, 2024
Study Registration Dates
First Submitted
August 26, 2022
First Submitted That Met QC Criteria
August 28, 2022
First Posted (Actual)
August 31, 2022
Study Record Updates
Last Update Posted (Actual)
August 31, 2022
Last Update Submitted That Met QC Criteria
August 28, 2022
Last Verified
August 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Neoplasms, Squamous Cell
- Esophageal Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Esophageal Squamous Cell Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Paclitaxel
- Cisplatin
Other Study ID Numbers
- NCC3649
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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