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

• Status: Not yet recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Collaborator: BeiGene
• Treatments: Carboplatin; Pemetrexed

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.