Clinical Trials /

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

NCT04507217

Description:

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

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous NSCLC
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BGB-A317-2003-IIT
  • NCT ID: NCT04507217

Conditions

  • NSCLC Stage IV
  • Brain Metastases
  • PD-1 Antibody

Interventions

DrugSynonymsArms
Tislelizumab, Carboplatin, PemetrexedBM with prior radiotherapy

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
BM without prior radiotherapyExperimentalNo Prior Systemic treatment for Stage IV NSQ-NSCLC With asymptomatic untreated BM
  • Tislelizumab, Carboplatin, Pemetrexed
BM with prior radiotherapyExperimentalNo Prior Systemic treatment for Stage IV NSQ-NSCLC With Clinical stable BM with prior radiotherapy
  • Tislelizumab, Carboplatin, Pemetrexed

Eligibility Criteria

        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, 8th
             Edition.

          2. Imaging confirmed brain metastases

          3. No prior systemic treatment for metastatic NSCLC

          4. Subjects with asymptomatic untreated brain metastases: no neurological symptoms, no
             requirements for corticosteroids, no surrounding edema, and no lesion >1.5 cm)

          5. Subjects with previously treated brain metastases: clinically stable for at least 2
             weeks, have no evidence of new or enlarging brain metastases, and be off steroids 3
             days prior to trial initiation as per local site assessment.

          6. ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.

          7. Have at least one measurable extracranial target lesion (per RECIST 1.1)

          8. Life expectancy ≥ 3 months

          9. Have adequate organ function as indicated by the following laboratory values

        Exclusion Criteria:

          1. Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints
             inhibitors.

          2. Received prior systemic cytotoxic chemotherapy for advanced disease

          3. Have activating EGFR mutations or ALK gene rearrangements

          4. Have brain metastases that is suitable for surgical resection

          5. Treatment with any approved systemic anti-cancer therapy or systemic
             immune-stimulatory agents (including but not limited to interferons, interleukin IL-2,
             and tumor necrosis factor) within 28 days prior to initiation of study treatment.

          6. Clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or
             abdominal tapping for drainage within 2 weeks prior to initiation of study treatment.

          7. Have Active leptomeningeal metastasis.

          8. History of allergic reactions to any study drugs.

          9. CrCl < 45 mL/min

         10. Patients with active viral hepatitis that requires treatment.

         11. Active autoimmune diseases that requires treatment and may affect study treatment
             estimated by investigator.

         12. Any condition that required systemic treatment with either corticosteroids or any
             other immunosuppressive medication that may affect study treatment estimated by
             investigator.

         13. Severe chronic or active infections requiring systemic antibacterial, anti-fungal or
             antiviral therapy.

         14. With a history of interstitial lung disease, non-infectious pneumonitis, or
             uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis,
             acute lung diseases, etc.

         15. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug
             abuse or dependence that would be unfavorable for the administration of study drug or
             affect the explanation of drug toxicity or AEs (Adverse Events) or result in
             insufficient or might impair compliance with study conduct.

         16. Concurrent participation in another clinical study.

         17. Pregnant, breastfeed, or expect to conceive or father children within the projected
             duration of the study.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) rate at 12 months according to RECIST v1.1
Time Frame:12months
Safety Issue:
Description: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 Outcome Measures

Measure:Objective Response Rate (ORR) according to RECIST v1.1
Time Frame:36 months
Safety Issue:
Description:ORR is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).
Measure:Progression-free survival (PFS) according to RECIST v1.1
Time Frame:36 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:36 months
Safety Issue:
Description:OS is defined as the time from the starting date of study drug to the date of death due to any cause
Measure:Progression-free survival 2 (PFS2)
Time Frame:36 months
Safety Issue:
Description: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
Measure:Duration of Response (DoR) according to RECIST v1.1
Time Frame:36 months
Safety Issue:
Description: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
Measure:Incidence and severity of treatment-emergent AEs (TEAEs)
Time Frame:36 months
Safety Issue:
Description:TEAEs graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
Measure:Neurocognitive impairment
Time Frame:36 months
Safety Issue:
Description:Neurocognitive impairment according to Hopkins Verbal Learning Test-Revised(HVLT-R)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sun Yat-sen University

Last Updated

August 12, 2020