- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04220307
A Study of a PD-1/CTLA-4 Bispecific Antibody AK104 in Patients With Metastatic Nasopharyngeal Carcinoma
October 10, 2022 updated by: Akeso
A Single-arm, Open-label, Multicenter, Phase II Study of AK104 in Patients With Metastatic Nasopharyngeal Carcinoma Who Have Progressed After At Least 2 Prior Lines of Chemotherapy
This is a single-arm, open-label, multicenter, phase II study to evaluate the anti-tumor activity, PK and immunogenicity of AK104 in patients with metastatic nasopharyngeal carcinoma who have progressed after at least 2 prior lines of systemic chemotherapy (of which one of them must be platinum-based chemotherapy).
Study Overview
Study Type
Interventional
Enrollment (Actual)
34
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 Locations
-
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Guangdong
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Guangzhou, Guangdong, China, 528403
- Sun Yat-sen University Cancer Center
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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
18 years to 75 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Signed written informed consent form voluntarily.
- Age over 18 years old (inclusive) and not more than 75 years old (inclusive), when signing the ICF.
- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
- Expected life expectance ≥ 3 months.
- Histologically confirmed diagnosis of nonkeratinizing differentiated or undifferentiated NPC.
- Not suitable for radical local therapy.
- Stage IVb metastatic NPC patients who have failed the first-line platinum-based chemotherapy and the second-line chemotherapy.
- At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously treated with local therapies such as radiotherapy can be considered a target lesion if there is objective evidence of progression in the lesion.
- Subjects must provide an available tumor tissue sample taken within 3 years prior to enrollment.
- Adequate organ function.
- Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception.
- Nonsterilized males who are sexually active with a female partner of childbearing potential must use highly effective method of contraception from Day 1 and for 120 days after the last dose of investigational product
Exclusion Criteria:
- Receipt of last radiotherapy or any anti-tumor treatment [chemotherapy, targeted therapy] within 3 weeks prior to the first dose of study treatment, Receipt of last Chinese herbal drugs with antitumor indications within 1 week prior to the first dose of study treatment.
- Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g. CD40, CD137, GITR and OX40 etc).
- Other invasive malignancies within 5 years, except for locally treatable (manifested as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
- Subjects with active autoimmune disease that requires systematic treatment in the past two years, with the exceptions of the following: vitiligo, alopecia, Grave disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of hormone replacement therapy and type I diabetes only requiring steady doses of insulin replacement therapy, or completely relieved childhood asthma that requires no intervention in adulthood, or primary diseases that will not relapse unless triggered by external factors.
- Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
- Subjects who require systemic corticosteroids (a dose equivalent to >10 mg/day prednisone) or other immunosuppressive drugs within 7days prior to the first dose of study drug.
- Known history of testing positive for human immunodeficiency virus (HIV).
- Known history of primary immunodeficiency virus infection.
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- History of gastrointestinal perforation and/ or fistula within 6 months prior to enrollment.
- Necrotic lesion(s) found by examinations within 4 weeks prior to enrollment, which, in the investigator's opinion, is at risk of massive bleeding.
- Known history of interstitial lung disease.
- Known history of active tuberculosis (TB).
- Serious infections within 4 weeks prior to the first dose of study drug, including but not limited to complications requiring hospitalization, sepsis or severe pneumonia.
- An active infection requiring systemic therapy.
- Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 1000 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <1000 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.
- Major surgery (as defined by the investigator) within 30 days prior to the first dose of study drug.
- Presence of meningeal metastasis, or active brain metastasis.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria, with the exception of alopecia.
- Receipt of live attenuated vaccination within 30 days prior to the first dose of study treatment, or plan to receive live attenuated vaccine during the study.
- Known history of severe hypersensitivity to other monoclonal antibodies.
- Known allergic reactions to any ingredients of AK104
- Pregnant or lactating women.
- Any conditions that, in the investigator's opinion, may put subjects treated with the study drug at risks, or interfere with the evaluation of study drug or subject safety, or the interpretation of study results
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: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: AK104 6 mg/kg
AK104 IV every 2 weeks (q2w)
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Subjects will receive AK104 by intravenous administration
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EXPERIMENTAL: AK104 15 mg/kg
AK104 IV every 3 weeks (q3w)
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Subjects will receive AK104 by intravenous administration
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: up to 2 years
|
ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1
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up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: up to 2 years
|
PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1 criteria) or death from any cause (whichever occurs first)
|
up to 2 years
|
Observed concentrations of AK104
Time Frame: From first dose of AK104 through 90 days after last dose of AK104
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The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration
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From first dose of AK104 through 90 days after last dose of AK104
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Number of subjects who develop detectable anti-drug antibodies (ADAs)
Time Frame: From first dose of AK104 through 90 days after last dose of AK104
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The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs)
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From first dose of AK104 through 90 days after last dose of AK104
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Disease control rate (DCR)
Time Frame: up to 2 years
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DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1
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up to 2 years
|
Duration of response (DoR)
Time Frame: up to 2 years
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DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first
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up to 2 years
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Overall survival (OS)
Time Frame: up to 2 years
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OS is defined as the time from the date of first dosing to death from any cause
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up to 2 years
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Incidence of treatment-emergent adverse events (TEAEs)
Time Frame: From the time of informed consent signed through 90 days after last dose of AK104
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An adverse event (AE) is any untoward medical occurrence or the deterioration of existing medical event in a clinical study subject administered an investigational drug, which does not necessarily have an unequivocal causal relationship with the investigational product
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From the time of informed consent signed through 90 days after last dose of AK104
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Ruihua Xu, MD, Sun Yat-sen University
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 (ACTUAL)
April 26, 2020
Primary Completion (ACTUAL)
May 15, 2021
Study Completion (ACTUAL)
August 23, 2022
Study Registration Dates
First Submitted
January 4, 2020
First Submitted That Met QC Criteria
January 4, 2020
First Posted (ACTUAL)
January 7, 2020
Study Record Updates
Last Update Posted (ACTUAL)
October 12, 2022
Last Update Submitted That Met QC Criteria
October 10, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Pharyngeal Neoplasms
- Otorhinolaryngologic Neoplasms
- Head and Neck Neoplasms
- Nasopharyngeal Diseases
- Pharyngeal Diseases
- Stomatognathic Diseases
- Otorhinolaryngologic Diseases
- Nasopharyngeal Neoplasms
- Carcinoma
- Nasopharyngeal Carcinoma
Other Study ID Numbers
- AK104-204
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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