Tislelizumab Plus Chemotherapy as First-Line Treatment for Advanced Squamous NSCLC With Brain Metastases

Study Overview
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Brief Summary
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This study is a prospective, single-arm, phase II clinical study to evaluate the efficacy and safety of Tislelizumab Plus Chemotherapy in patients with squamous NSCLC with brain metastases who had not previously received systemic therapy.

Official Title
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A Phase II, Prospective Clinical Study to Evaluate the Efficacy and Safety of Tislelizumab Plus Chemotherapy as First-Line Treatment in Patients With Brain Metastases of Squamous Non-small Cell Lung Cancer

Conditions
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Non-Small Cell Squamous Lung Cancer, Brain Metastases

Intervention / Treatment
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* Drug: Tislelizumab, paclitaxel, Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed squamous non-small cell lung cancer; Asymptomatic brain metastases or brain metastases that are relieved by dehydration therapy and remain clinically stable for at least 2 weeks MRI confirmed tumor parenchymal metastases, ≥ 3 brain lesions; or patients with 1-2 brain lesions but do not require local treatment or refuse local treatment. At least one measurable lesion in the brain lesion must be ≥ 5mm in diameter; patients with local meningeal metastasis are allowed, but those with extensive meningeal metastasis are not included Patients with stable brain metastasis symptoms after stereotactic radiotherapy are allowed (the number of stereotactic radiotherapy lesions is not more than 3) No prior systemic treatment for metastatic NSCLC Tumor tissue biomarker detection results must meet the following conditions at the same time: （1）EGFR mutation negative.（2）ALK rearrangement negative.（3）There are sufficient tissue samples for PD-L1 detection Aged ≥ 18 years and ≤ 75 years ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1 Life expectancy of more than 3 months Have adequate organ function as indicated by the following laboratory values Written informed consent before any trial-related procedures are performed Exclusion Criteria: Subjects with any of the following criteria may not be included in this study: With mixed adenosquamous carcinoma or small cell lung cancer mainly composed of adenocarcinoma Currently participating in interventional clinical study treatment, or have received other investigational drugs or investigational device treatment before the first dose; Received prior therapies targeting PD-1, PD-L1, CTLA-4, cytotoxic chemotherapy or other immune checkpoints inhibitors Received solid organ or blood system transplantation Have active autoimmune diseases requiring systemic therapy within 2 years before the first dose Diagnosis of immunodeficiency or systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of the study History of non-infectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year before the first dose Known history of human immunodeficiency virus (HIV) infection Untreated active hepatitis B; Note: hepatitis B subjects who meet the following criteria are also eligible: a) HBV viral load must be < 1000 copies/ml before the first dose, and subjects should receive anti-HBV therapy to avoid viral reactivation throughout the study chemotherapy drug treatment b) For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but viral reactivation needs to be closely monitored; Subjects with active HCV infection Pregnant and lactating women Malignant tumors other than NSCLC within 5 years before screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell epithelial skin cancer, local prostate cancer after radical resection, and ductal carcinoma in situ after radical resection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tislelizumab plus chemotherapy<br> | Drug: Tislelizumab, paclitaxel, Carboplatin<br>* Tislelizumab, 200mg administered intravenously (IV) on Day 1 of each 21-day cycle paclitaxel 175 mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle, 4-6cycle Carboplatin AUC 5 administered intravenously (IV) on Day 1 of each 21-day cycle, 4-6 cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intracranial progression-free survival (iPFS) after treatment with tislelizumab plus chemotherapy in patients with asymptomatic brain metastases or stable symptoms after stereotactic radiotherapy (according to RECIST 1.1) | Intracranial Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of intracranial disease progression or death, whichever occurs first | 12months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intracranial objective response rate (iORR) (according to RECIST 1.1) | iORR is defined as the proportion (%) of patients with complete or partial response of intracranial lesions | 12months | 
| objective response rate (ORR) (according to RECIST 1.1) | ORR is defined as the proportion (%) of patients with complete or partial response of overall lesions | 12months | 
| progression-free survival (PFS) (according to RECIST 1.1) | Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of overall disease progression or death, whichever occurs first. | 12months | 
| overall survival (OS) (according to RECIST 1.1) | OS is defined as the time from the starting date of study drug to the date of death due to any cause | 24months | 
| Safety of treatment was assessed using NCI-CTCAEv5 version | TEAEs graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 | 24months | 
| Assessment of neurocognitive deterioration | Neurocognitive impairment according to Hopkins Verbal Learning Test-Revised（HVLT-R) | 24months |