Non-Small Cell Lung Cancer
Conditions
Brief summary
The study aims to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab versus chemotherapy in combination with pembrolizumab in the first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC with PD-L1 negative.
Detailed description
This is a randomized, open-label, multicenter, Phase 3 study to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab versus chemotherapy in combination with pembrolizumab in the first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC with PD-L1 negative.
Interventions
DRUGSKB264
IV Infusion
DRUGPembrolizumab
IV Infusion
DRUGpemetrexed
IV Infusion
IV Infusion
Sponsors
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomised in a 1:1 ratio to one of two intervention groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed non-squamous NSCLC, and unsuitable for radical surgery and/or radical concurrent/sequential radiochemotherapy, locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC; 2. EGFR-sensitive mutation negative \[no exon 19 deletion (19-Del) or exon 21 point mutation (L858R mutation)\] and ALK fusion gene negative, without known ROS1 gene fusion, NTRK gene fusion, BRAF V600E mutation, etc. that have been approved for targeted therapy driving gene alterations; 3. No prior systemic anti-cancer therapy for locally advanced or metastatic NSCLC; 4. Participants whose tumours are PD-L1 TPS \< 1%; 5. At least one measurable lesion per RECIST v1.1; 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with no worsening within 7 days prior to randomization; 7. A life expectancy of at least 12 weeks; 8. Adequate organ and bone marrow function;
Exclusion criteria
1. Histologically or cytologically confirmed tumors with a component of small cell lung cancer, neuroendocrine carcinoma, sarcomatoid carcinoma, or squamous cell carcinoma exceeding 10%; 2. Previously received immune checkpoint inhibitors,checkpoint agonists or any treatment targeting the immune mechanism of tumors such as immune cell therapy; 3. Active second malignancy; 4. Symptomatic or uncontrolled cardiovascular disease，serious thromboembolic； 5. History of noninfectious pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD; 6. Active infection requiring systemic therapy within 2 weeks of randomization; 7. Active hepatitis B or hepatitis C virus infection; 8. Human immunodeficiency virus (HIV) positive or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection; 9. Major surgery within 4 weeks prior to randomization or expected major surgery during the study; 10. Pregnant or lactating women;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) | Randomization up to approximately 28 months | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Randomization up to approximately 43 months | OS is defined as the time from randomization until the date of death due to any cause. |
| Progression-Free Survival (PFS) assessed by Investigator | Randomization up to approximately 28 months | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator or death due to any cause, whichever occurs first. |
| Objective Response Rate (ORR) | Randomization up to approximately 28 months | ORR is defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by BICR/investigator per RECIST 1.1 |
| Disease control rate (DCR) | Randomization up to approximately 28 months | DCR is defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by BICR/ investigator per RECIST 1.1 |
| Duration of Response (DoR) | Randomization up to approximately 28 months | DoR is defined as the time from the date of first documented CR or PR until date of documented disease progression per RECIST 1.1, as assessed by BICR/investigator or death due to any cause, whichever occurs first. |
| Time to Response (TTR) | Randomization up to approximately 28 months | TTR is defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR/investigator per RECIST 1.1. |
| AEs and SAEs | All AEs should be observed and recorded from the first dose until 30 days after the last dose. SAEs were observed and recorded until 90 days after the last dose of pembrolizumab or 30 days after the last dose of SKB264,whichever occurred later. | Incidence and severity of AEs and SAEs (per CTCAE v5.0), and clinically significant abnormal laboratory results |
| Health-Related Quality of Life Assessed by EORTC QLQ-C30 | Randomization up to approximately 28months | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is used to assess participants's health-related quality of life. The scale covers functional domains, symptom domains, and overall health status/total quality of life domain. All domain scores are standardized to a range of 0 to 100. For functional domains and overall health status/total quality of life, higher scores indicate better functional status and quality of life; for symptom domains, higher scores indicate more symptoms or problems (worse quality of life). This study will compare changes from baseline in quality-of-life scores across all dimensions, analyze time to deterioration in general health status, symptoms and function, and summarize the number and percentage of participants with clinically meaningful changes post-baseline. |
| Lung Cancer-Related Symptoms Assessed by EORTC QLQ-LC13 Symptom Domain | From randomization up to approximately 28 months | The symptom domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13) is used to assess lung cancer-related symptoms and treatment-related symptoms. The scale includes both multiple-item and single-item measurement parameters. Scores are standardized to a range of 0 to 100. Higher scores indicate more severe symptoms (worse outcome). This study will compare changes from baseline in symptom scores, analyze time to deterioration of cancer-related symptoms, and summarize the number and percentage of participants with clinically meaningful changes post-baseline. |
| PK | Randomization up to approximately 28months | PK parameters of SKB264-ADC, SKB264-TAB and free KL610023, such as maximum concentration (Cmax), minimum concentration (Cmin ), etc. |
| Immunogenicity | Randomization up to approximately 28months | Anti-drug antibody (ADA) of SKB264 in the serum of subjects will be determined using MSD-based Bridging-ECLA. |
| Biomarkers | Tumor tissue samples should be provided for TROP2 testing after subjects are eligible for screening. | Correlation between the expression level of TROP2 in tumor tissues and the efficacy. |
Countries
China
Outcome results
None listed