Locally Advanced or Metastatic NSCLC
Conditions
Brief summary
This is a randomized, double-blind, phase III clinical study to compare the efficacy and safety of AK104 combined chemotherapy versus Tislelizumab combined chemotherapy in first-line treatment of Locally advanced or metastatic NSCLC with PD-L1 TPS \< 1%.
Interventions
DRUGAK104
AK104 IV, q3w
DRUGTislelizumab
Tislelizumab IV, q3w
DRUGcarboplatin
carboplatin IV, q3w
DRUGPemetrexed
Pemetrexed IV, q3w (for Nonsquamous NSCLC)
DRUGPaclitaxel
Paclitaxel IV, q3w (for squamous NSCLC)
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subjects voluntarily participated in the study with full informed consent and signed written informed consent form. 2. Aged ≥18 years when the subject signed the informed consent. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Life expectancy ≥ 3 months. 5. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) that not amenable to complete surgical resection and not amenable to radical concurrent/sequential chemoradiation or metastatic (Stage IV) NSCLC (American Joint Committee on Cancer \[AJCC\] 8th edition). 6. No prior systemic therapy for advanced or metastatic NSCLC was received. 7. PD-L1 TPS \< 1%. 8. No EGFR sensitive mutations or ALK gene translocation alterations.
Exclusion criteria
1. Histologically confirmed small cell lung cancer (SCLC). 2. NSCLC with driver gene mutations for approved targeted drug indications. 3. Active central nervous system (CNS) metastases were present. 4. Pulmonary radiation therapy \> 30 Gy within 6 months prior to first dose. 5. Active malignant tumors within the past 5 years, except for tumors in this study and scured local tumors. 6. Pregnant or lactating women. 7. Clinically significant cardiovascular or cerebrovascular disease. 8. Subjects with a known history of severe hypersensitivity to other monoclonal antibodies. A known history of allergy or hypersensitivity to all investigational drugs or any of their components. 9. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or autoimmune diseases that may relapse or require scheduled treatment as judged by the Investigator. 10. Known active pulmonary tuberculosis. 11. Patients with active hepatitis B or active hepatitis C. 12. Known medical history of immunodeficiency or positive HIV test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival(OS) | Through Database Cutoff Date (Up to approximately 39 months) | OS is defined as the time from randomization to death due to any cause. |
| Progression-Free Survival(PFS) by investigator(INV) | Through Database Cutoff Date (Up to approximately 39 months) | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) was assessed by INV | Through Database Cutoff Date (Up to approximately 39 months) | Disease control rate (DCR) was assessed based on RECIST V1.1 criteria |
| Time to response (TTR) was assessed by INV | Through Database Cutoff Date (Up to approximately 39 months) | The time from the first administration to the date of documented CR or PR |
| Duration of response (DOR) was assessed by INV | Through Database Cutoff Date (Up to approximately 39 months) | Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria |
| Objective response rate (ORR) was assessed by BIRC | Through Database Cutoff Date (Up to approximately 39 months) | ORR is the proportion of subjects with CR or PR based on RECIST v1.1 |
| Disease control rate (DCR) was assessed BIRC | Through Database Cutoff Date (Up to approximately 39 months) | Disease control rate (DCR) was assessed based on RECIST V1.1 criteria |
| Time to response (TTR) was assessed by BIRC | Through Database Cutoff Date (Up to approximately 39 months) | The time from the first administration to the date of documented CR or PR |
| Progression-Free Survival(PFS) by Blind independent center review(BIRC) | Through Database Cutoff Date (Up to approximately 39 months) | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 |
| The number of subjects experiencing adverse events (AEs) | Through Database Cutoff Date (Up to approximately 39 months) | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results. |
| Pharmacokinetic | Through Database Cutoff Date (Up to approximately 39 months) | The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration |
| Antidrug antibodies (ADA) of AK104 | Through Database Cutoff Date (Up to approximately 39 months) | Proportion of subjects who develop detectable anti-drug antibodies (ADAs) |
| Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Through Database Cutoff Date (Up to approximately 39 months) | EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, Not at all; 2, A little; 3, Quite a bit; to 4, Very much. Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms. |
| Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29) | Through Database Cutoff Date (Up to approximately 39 months) | EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, Not at all; 2, A little; 3, Quite a bit; to 4, Very much. For symptoms scales, higher scores indicated greater symptom burden. |
| Duration of response (DOR) was assessed by BIRC | Through Database Cutoff Date (Up to approximately 39 months) | Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria |
| Objective response rate (ORR) was assessed by INV | Through Database Cutoff Date (Up to approximately 39 months) | ORR is the proportion of subjects with CR or PR based on RECIST v1.1 |
Countries
China
Contacts
Primary ContactZhifang Yao, M.D.
Outcome results
None listed