Tislelizumab Combined With Chemotherapy With or Without Bevacizumab in TKI-Resistant EGFR-Mutated Non-squamous NSCLC

  • STATUS
    Recruiting
  • End date
    Mar 29, 2025
  • participants needed
    120
  • sponsor
    Shanghai Chest Hospital
Updated on 29 November 2021
paclitaxel
tyrosine
icotinib
growth factor
kinase inhibitor
pemetrexed
carboplatin
erlotinib
epidermal growth factor receptor
EGFR
bevacizumab
cancer chemotherapy
epidermal growth factor
afatinib
gefitinib
osimertinib
lung carcinoma
egfr t790m
squamous non-small cell lung cancer
non-squamous non-small cell lung cancer

Summary

A phase II, open-label, multicenter, two cohorts, prospective clinical study to investigate the efficacy and safety of tislelizumab (anti-pd1 antibody) combined with chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer patients with EGFR sensitizing mutation who failed EGFR TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) therapy.

Description

Although EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the efficacy and safety of tislelizumab plus carboplatin and Nab-paclitaxelcohort 1or tislelizumab plus Nab-paclitaxel and bevacizumab cohort 2 in EGFR-mut nsq-NSCLC pts failed to EGFR TKI therapies.

Details
Condition nsclc, Non-Small Cell Lung Cancer
Treatment carboplatin, bevacizumab, Pemetrexed, nab paclitaxel, tislelizumab, Carboplatin and Nab-paclitaxel
Clinical Study IdentifierNCT04405674
SponsorShanghai Chest Hospital
Last Modified on29 November 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically or cytologically confirmed, locally advanced (Stage IIIB/C) not amenable to curative surgery or radiotherapy, or metastatic (Stage IV) non-squamous NSCLC according to American Joint Committee on Cancer, 8th Edition
Documentation of tumor EGFR sensitizing mutation before EGFR TKI treatment, including 19del, L858R, G719X, S786I and L861Q
Disease progression after treatment with an EGFR TKI therapy: 1) Patients previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib/icotinib) are required to provide specimens after PD to confirmed absence of EGFR T790M mutation; 2) Patients with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib/icotinib) are required to have 3rd generation EGFR TKI (e.g. osimertinib) treatment failure prior to enrollment; 3) Patients previously failed from 3rd generation EGFR TKI (e.g. osimertinib) treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status
ECOG (Eastern Cooperative Oncology Group) performance status 1
Life expectancy 3 months
Adequate organ function
Able to provide written informed consent by the patient or by the patient's legally acceptable representative and can understand and agree to comply with the requirements of the study
18 to 75 years old on the day of signing the ICF (Informed Consent Form)

Exclusion Criteria

Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints
Received prior platinum-based chemotherapy for advanced disease
Patients who have received prior systemic anti-vascular therapy (e.g., bevacizumab and small molecule VEGFR inhibitors) for advanced disease (Cohort 2)
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
Clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or abdominal tapping for drainage within 2 weeks prior to initiation of study treatment
Received EGFR TKI treatment within 2 weeks
Active leptomeningeal disease or uncontrolled brain metastasis
History of allergic reactions to any study drugs
CrCl < 45 mL/min
Patients with active viral hepatitis that requires treatment
Active autoimmune diseases that requires treatment and may affect study treatment estimated by investigator
Any condition that required systemic treatment with either corticosteroids or any other immunosuppressive medication that may affect study treatment estimated by investigator
Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy
With a history of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc
Any major surgical procedure requiring general anesthesia 28 days before initiation of study treatment
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
History of hemoptysis, i.e., coughing up at least one-half teaspoon of fresh blood, within 3 months prior to enrollment. (Cohort 2)
Concurrent participation in another clinical study
Imaging shows tumor invasion of a large vessel (e.g., pulmonary artery or superior vena cava) that the investigator determines is at risk for bleeding. (Cohort 2)
Had minor surgical procedures, such as tube placement, within 48 hours prior to first bevacizumab treatment. (Cohort 2)
Recently treated with a full dose oral or parenteral anticoagulant or thrombolytic agent. Prophylactic using anticoagulants is allowed. (Cohort 2)
History or test results indicating an inherited bleeding tendency or coagulation disorder that may increase the risk of bleeding (cohort 2)
uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg) (cohort 2)
Clinically meaningful (e.g., active) cardiovascular disease that, in the judgment of the investigator, is intolerant to bevacizumab therapy (cohort 2)
Non-cured wound, peptic ulcer in active phase, or fracture (cohort 2)
History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or thrombotic disease within 6 months judged by the investigator to be intolerant to bevacizumab treatment (Cohort 2)
Have known human immunodeficiency virus (HIV) infection
Pregnant or lactating women, or male and female patients who plan to have children during the study period. -
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