Brain Metastases, NSCLC Stage IV, PD-1 Antibody
Conditions
Brief summary
This is a phase II, Open-Label, Multicenter, Prospective Clinical Study to Investigate the Efficacy and Safety of Tislelizumab Combined with Pemetrexed/ Carboplatin in Patients with Brain Metastases of Non-squamous Non-small Cell Lung Cancer. The primary end point is PFS, and secondary endpoint is ORR, OS, DoR and Neurocognitive impairment. during the study, the exploratory objectives including (1) PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment (2) Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1 and RANO-BM
Interventions
Tislelizumab: 200mg administered intravenously (IV) on Day 1 of each 21-day cycle Carboplatin: AUC 5 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles Pemetrexed: 500mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Tislelizumab Combined with Pemetrexed/ Carboplatin
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Disease-related inclusion criteria: 1. Histologically confirmed metastatic (Stage IV) not amenable to curative surgery or radiotherapy, non-squamous NSCLC according to American Joint Committee on Cancer (AJCC), 8th Edition. 2. Radiographically confirmed brain metastases; 3. No prior systemic treatment for stage IV NSCLC. (Bevacizumab administered for improving radiation-induced encephaledema during irradiating intracranial lesions is not considered as systemic therapy for stage IV NSCLC) 4. Patients with asymptomatic BM or symptoms can be controlled by low dose corticosteroids (≤ 10 mg/day of prednisone or equivalent) or antiepileptics drugs; 5. Patients with previous local treatment to BMs should be stable and suitable to receive the systemic treatment; 6. ECOG PS: 0 \ 1 7. Extracranial measurable target lesions (per RECIST v1.1) 8. Life expectancy ≥ 3 months Have adequate hematology, clinical chemistry, and organ function as indicated by the following laboratory values (confirmed within 7 days prior to the first dose): 9. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L. 10. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × upper limit of normal \[ULN\]. 11. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. 12. Serum total bilirubin ≤ 1.5 × ULN (total bilirubin must be \< 3 × ULN for patients with Gilbert's syndrome). 13. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or AST and ALT ≤ 5 × ULN for patients with liver metastases. General inclusion criteria: 14. Able to provide written ICF signed by patient or by his/her legally authorized representative or guardian and can understand and agree to comply with the study protocol and follow-up procedures. 15. Male or female, aged 18 \ 75 years on the day of signing ICF. Female patients of childbearing potential and non-sterile male patients must be willing to use a highly effective method of birth control for the duration of the study and for at least 120 days after the last dose of tislelizumab.
Exclusion criteria
Disease-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) rate at 12 months according to RECIST v1.1 | 12months | Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) according to RECIST v1.1 | 36 months | ORR is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR). |
| Progression-free survival (PFS) according to RECIST v1.1 | 12 months | Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first. |
| Overall Survival (OS) | 36 months | OS is defined as the time from the starting date of study drug to the date of death due to any cause |
| Duration of Response (DoR) according to RECIST v1.1 | 36 months | DoR is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first |
| Incidence and severity of treatment-emergent AEs (TEAEs) | 36 months | TEAEs graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 |
| Neurocognitive impairment | 36 months | Neurocognitive impairment according to Hopkins Verbal Learning Test-Revised（HVLT-R） |
| Progression-free survival (PFS) according to RANO-BM | 36 months | PFS2 is defined as the time from first intracranial disease progression to second/subsequent disease progression (intracranial or extracranial) after initiation of new anti-cancer therapy, or death from any cause, whichever occurs first |
Other
| Measure | Time frame |
|---|---|
| PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment | 36 months |
Countries
China
Outcome results
None listed