A Study of AK104 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
Primary Purpose
Lung Cancer Non-Small Cell Stage IIIB/IIIC/IV
Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
AK104 plus Carboplatin and Pemetrexed
AK104 plus Carboplatin and paclitaxel
Sponsored by

About this trial
This is an interventional treatment trial for Lung Cancer Non-Small Cell Stage IIIB/IIIC/IV
Eligibility Criteria
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 informed consent form.
- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
- Expected life expectance ≥ 3 months.
- Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC.
- No prior systemic chemotherapy for advanced or metastatic NSCLC. Subjects who have received prior adjuvant chemotherapy or neoadjuvant chemotherapy with curative intent, or definitive chemoradiotherapy for advanced disease, will be eligible provided that progression has occurred >6 months from last treatment.
- At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously irradiated will not be considered a target lesion.
- Subjects must provide an available tumor tissue sample taken < 1 year prior to first dose of study treatment.
- Subjects must provide wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) reported by tissue-based tests(for non-squamous NSCLC subjects only).
- 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.
Key Exclusion Criteria:
- Subjects who are diagnosed as NSCLC that harbors an epidermal growth factor receptor (EGFR)-sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
- Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible
- Received prior treatment with EGFR inhibitors or ALK inhibitors.
- Is currently participating intervention study or has participated in a study of an investigational agent or investigational device within 4 weeks prior to administration of AK104.
- 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 Inducible T-cell co-stimulator (ICOS) or agonists (e.g. CD40, CD137, GITR and OX40 etc).
- Subjects who received non-thoracic radiotherapy >30 Gy within 4 weeks prior to the first dose , or thoracic radiotherapy >30 Gy within 24 weeks prior to the first dose study drug.
- Other active malignancies within 2 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, known or suspected autoimmune disease, or a medical history of autoimmune disease,
- Subjects who require systemic corticosteroids (a dose equivalent to >10 mg/day prednisone) or other immunosuppressive drugs within 14 days prior to administration of AK104.
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
- Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
- Known history of active tuberculosis (TB).
- 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.
- Known history of testing positive for human immunodeficiency virus (HIV).
- Presence of meningeal metastasis, spinal cord compression, leptomeningeal disease 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 vaccination within 30 days of planned treatment start, or plan to receive live vaccine during the study.
- Known history of server hypersensitivity to other monoclonal antibodies.
- Known severe allergic reactions to pemetrexed, paclitaxel, carboplatin or platinum-containing component, or their preventive medications.
- Known allergic reactions to any ingredients of AK104.
- Known history of substance abuse, or alcohol abuse
- 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.
Sites / Locations
- Sun Yat-Sen University Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Nonsquamous NSCLC
Squamous NSCLC
Arm Description
Outcomes
Primary Outcome Measures
The number of subjects experiencing adverse events (AEs) (Phase Ib)
Objective response rate (ORR) assessed by investigator
Secondary Outcome Measures
Disease control rate (DCR)
Duration of response (DoR)
Progression-free survival (PFS)
Overall survival (OS)
Time to response (TTR)
Minimum observed concentration (Cmin) of AK104 at steady state
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04647344
Brief Title
A Study of AK104 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
Official Title
An Open-label, Multicenter, Phase Ib/II Study of AK104, Combined Chemotherapy as First-line Therapy to Treat Locally Advanced or Metastatic Non-small Cell Lung Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 24, 2020 (Actual)
Primary Completion Date
February 8, 2023 (Anticipated)
Study Completion Date
April 8, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akeso
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase Ib/II , open-label, multicenter single arm study designed to evaluate the efficacy, safety, tolerability, pharmacokinetic (PK), and immunogenicity of AK104 combined with Carboplatin and Pemetrexed/ Paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer Non-Small Cell Stage IIIB/IIIC/IV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Nonsquamous NSCLC
Arm Type
Experimental
Arm Title
Squamous NSCLC
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AK104 plus Carboplatin and Pemetrexed
Intervention Description
Subjects receive AK104 15mg/kg intravenously (IV) plus pemetrexed 500 mg/m^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK104 15mg/kg IV plus pemetrexed 500 mg/m^2 IV Q3W until progression.
Intervention Type
Drug
Intervention Name(s)
AK104 plus Carboplatin and paclitaxel
Intervention Description
Subjects receive AK104 15mg/kg intravenously (IV) plus paclitaxel 175 mg/m^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK104 15mg/kg IV IV Q3W until progression.
Primary Outcome Measure Information:
Title
The number of subjects experiencing adverse events (AEs) (Phase Ib)
Time Frame
From the time of informed consent through 90 days following termination of treatment with investigational product
Title
Objective response rate (ORR) assessed by investigator
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Disease control rate (DCR)
Time Frame
Up to 2 years
Title
Duration of response (DoR)
Time Frame
Up to 2 years
Title
Progression-free survival (PFS)
Time Frame
Up to 2 years
Title
Overall survival (OS)
Time Frame
Up to 2 years
Title
Time to response (TTR)
Time Frame
Up to 2 years
Title
Minimum observed concentration (Cmin) of AK104 at steady state
Time Frame
From first dose of AK104 through 90 days after last dose of AK104
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 informed consent form.
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
Expected life expectance ≥ 3 months.
Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC.
No prior systemic chemotherapy for advanced or metastatic NSCLC. Subjects who have received prior adjuvant chemotherapy or neoadjuvant chemotherapy with curative intent, or definitive chemoradiotherapy for advanced disease, will be eligible provided that progression has occurred >6 months from last treatment.
At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously irradiated will not be considered a target lesion.
Subjects must provide an available tumor tissue sample taken < 1 year prior to first dose of study treatment.
Subjects must provide wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) reported by tissue-based tests(for non-squamous NSCLC subjects only).
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.
Key Exclusion Criteria:
Subjects who are diagnosed as NSCLC that harbors an epidermal growth factor receptor (EGFR)-sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible
Received prior treatment with EGFR inhibitors or ALK inhibitors.
Is currently participating intervention study or has participated in a study of an investigational agent or investigational device within 4 weeks prior to administration of AK104.
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 Inducible T-cell co-stimulator (ICOS) or agonists (e.g. CD40, CD137, GITR and OX40 etc).
Subjects who received non-thoracic radiotherapy >30 Gy within 4 weeks prior to the first dose , or thoracic radiotherapy >30 Gy within 24 weeks prior to the first dose study drug.
Other active malignancies within 2 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, known or suspected autoimmune disease, or a medical history of autoimmune disease,
Subjects who require systemic corticosteroids (a dose equivalent to >10 mg/day prednisone) or other immunosuppressive drugs within 14 days prior to administration of AK104.
Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
Known history of active tuberculosis (TB).
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.
Known history of testing positive for human immunodeficiency virus (HIV).
Presence of meningeal metastasis, spinal cord compression, leptomeningeal disease 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 vaccination within 30 days of planned treatment start, or plan to receive live vaccine during the study.
Known history of server hypersensitivity to other monoclonal antibodies.
Known severe allergic reactions to pemetrexed, paclitaxel, carboplatin or platinum-containing component, or their preventive medications.
Known allergic reactions to any ingredients of AK104.
Known history of substance abuse, or alcohol abuse
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li Zhang, MD
Organizational Affiliation
Sun Yat-sen University Cancer Center, Guangzhou, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-Sen University Cancer Center
City
Guanzhou
State/Province
Guangdong
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of AK104 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
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