Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous NSCLC

NCT04507217 | Completed Phase 2

• 1 other identifier: BGB-A317-2003-IIT
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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

Conditions

NSCLC Stage IV; Brain Metastases; PD-1 Antibody

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) rate at 12 months according to RECIST v1.1

  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

  12months

Secondary Outcomes (7)

• Objective Response Rate (ORR) according to RECIST v1.1

  36 months

• Progression-free survival (PFS) according to RECIST v1.1

  12 months

• Overall Survival (OS)

  36 months

• Progression-free survival (PFS) according to RANO-BM

  36 months

• Duration of Response (DoR) according to RECIST v1.1

  36 months

Other Outcomes (1)

• PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment

  36 months

Study Arms (1)

Eligible patients

EXPERIMENTAL

tislelizumab (200mg) in combination with pemetrexed (500mg/m2) and carboplatin (AUC=5) intravenously on day 1 of a 3-week cycle for 4 cycles. Afterwards, patients without disease progression were treated with maintenance treatment with tislelizumab (200mg) plus pemetrexed (500mg/m2) every 3 weeks up to 24 months or until disease progression, unacceptable toxicity, or death.

Drug: Tislelizumab, Carboplatin, Pemetrexed

Interventions

Tislelizumab, Carboplatin, Pemetrexed DRUG

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

Eligible patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Radiographically confirmed brain metastases;
• 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)
• Patients with asymptomatic BM or symptoms can be controlled by low dose corticosteroids (≤ 10 mg/day of prednisone or equivalent) or antiepileptics drugs;
• Patients with previous local treatment to BMs should be stable and suitable to receive the systemic treatment;
• ECOG PS: 0 \~ 1
• Extracranial measurable target lesions (per RECIST v1.1)
• 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):
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L.
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × upper limit of normal \[ULN\].
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• Serum total bilirubin ≤ 1.5 × ULN (total bilirubin must be \< 3 × ULN for patients with Gilbert's syndrome).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or AST and ALT ≤ 5 × ULN for patients with liver metastases.
• 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.

You may not qualify if:

• Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints inhibitors.
• Received prior systemic chemotherapy for advanced disease.
• Have EGFR mutation or ALK gene translocation.
• Patients iwith BMs that have received systemic treatment with corticosteroids (\>10 mg/day of prednisone or equivalent) or other drugs to relieve or prevent symptoms of BMs.
• Patients with intracranial metastases that are locally amenable.
• Have received any approved systemic anticancer therapy or systemic immunomodulators (including but not limited to interferon, interleukin-2, and tumor necrosis factor) within 4 weeks prior to the first dose of study drug.
• Have clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or abdominal tapping for drainage within 2 weeks prior to the first dose of study drugs.
• Active leptomeningeal metastasis.
• History of allergic reactions to any study drugs and their excipients.
• Creatinine clearance (Ccr) \< 45 mL/min.
• Patients with active viral hepatitis that requires treatment as judged by the investigator: a. chronic hepatitis B virus carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) (The HBV DNA test will be performed only for patients who have a positive antibody to hepatitis B core antigen (anti-HBc antibody) test); b. patients who have positive hepatitis C virus (HCV) RNA results (The HCV RNA test will be performed only for patients testing positive for HCV antibody).
• Active autoimmune diseases that requires systemic treatment and may impact study treatment as assessed by investigator.
• Any condition that required extensive chronic treatment with either corticosteroids or any other immunosuppressive medications that may impact study treatment as assessed by investigator.
• Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection, etc.; 1) Serious infections within 4 weeks before first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; 2) Receive therapeutic oral or intravenous antibiotics within 2 weeks before first dose. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
• Major surgery requiring general anesthesia within 4 weeks before first dose.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (2)

Cancer Center of Sun-Yat Sen University (CCSYSU)

Guangzhou, Guangdong, 510060, China

Location

Guangxi Medical University Affiliated Tumor Hospital

Nanning, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

tislelizumab; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Model Details: Tislelizumab Combined with Pemetrexed/ Carboplatin

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 11, 2020
• Study Start: September 15, 2020
• Primary Completion: November 15, 2022
• Study Completion: January 30, 2023
• Last Updated: May 25, 2023

Record last verified: 2023-05

Locations

CN (2)