Efficacy and Safety of Tislelizumab Combined With Bevacizumab and Platinum Plus Pemetrexed for Untreated EGFR+ and High PD-L1 Expression Non-squamous NSCLC :a Phase II, Single-center, Single Arm Study
Overview
- Phase
- Phase 2
- Intervention
- Tislelizumab Combined With Bevacizumab and Platinum Plus Pemetrexed
- Conditions
- Non-squamous Non-small Cell Lung Cancer
- Sponsor
- Sichuan Cancer Hospital and Research Institute
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- middle progression free survival
- Last Updated
- 3 years ago
Overview
Brief Summary
A study to evaluate the efficacy and safety of tislelizumab combined with bevacizumab and platinum-based pemetrexed in the treatment of naïve patients with advanced non-squamous non-small cell lung cancer with sensitive EGFR mutations and high PD-L1 expression Prospective, open-label, single-arm phase II clinical study
Detailed Description
A study to evaluate the efficacy and safety of tislelizumab combined with bevacizumab and platinum-based pemetrexed in the treatment of naïve patients with advanced non-squamous non-small cell lung cancer with sensitive EGFR mutations and high PD-L1 expression Prospective, open-label, single-arm phase II clinical study; Research purposes: Main purpose: To evaluate the median progression-free rate of tislelizumab combined with bevacizumab and platinum pemetrexed in treatment-naïve advanced non-small cell lung cancer patients with sensitive EGFR mutations and high PD-L1 expression Survival (middle progression free survival, mPFS) Secondary purpose: * Evaluation of objective response rate (ORR) according to RECIST version 1.1; * Evaluation of disease control rate (DCR) according to RECIST version 1.1; * Assess overall survival (OS); * Assess Duration of Response (DOR); * Evaluate the safety of the treatment using NCI-CTCAE v5; Exploratory Purpose: • Assess potential predictive biomarkers.
Investigators
Juan LI, MD
Director of standard treatment department of medical oncology
Sichuan Cancer Hospital and Research Institute
Eligibility Criteria
Inclusion Criteria
- •≥ 18 and ≤ 75 years of age. Signed the informed consent form prior to patient entry
- •Histologically or pathologically confirmed non-squamous non-small cell lung cancer(NSCLC) with stage IV /III
- •Patients with EGFR sensitive mutations: 19del and L858R who have not been treated with TKI for the first time, the patients need to provide the test results of the certified detection platform, and the PD-L1 expression based on tissue specimen detection is greater than 50% (PD-L1 detection clone number: SP263).
- •A World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) Performance Status Score (PS) of 0 or 1 at the time of recruitment.
- •Adequate organ and bone marrow function, defined as:
- •Hemoglobin≥9.0 g/dL
- •Absolute neutrophil count ≥1.5 × 109/L
- •Platelet count ≥100 × 109/L
- •Serum bilirubin ≤ 1.5 × upper limit of normal range (ULN). This does not apply to patients diagnosed with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia \[primarily unconjugated bilirubin\] without evidence of hemolysis or liver pathology), which may be allowed after consultation with a physician patients participating in the study.
- •ALT and AST ≤2.5 × ULN
Exclusion Criteria
- •Patients with grade ≥2 non-infectious pneumonia.
- •History of allogeneic organ transplantation, except corneal transplantation.
- •Active or previously documented autoimmune or inflammatory diseases (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[except diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatous vasculitis, Graves disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). Exceptions to this standard include:
- •Vitiligo or alopecia patients
- •Patients with hypothyroidism who are stable on hormone replacement therapy (eg, after Hashimoto's syndrome)
- •Any chronic skin disease that does not require systemic treatment
- •Patients without active disease within the past 5 years may be included in the study, but only after consultation with the study physician
- •Patients with celiac disease that can be controlled with diet alone
- •Uncontrolled concurrent diseases, including but not limited to: persistent or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmia, active ILD , Severe chronic gastrointestinal disease with diarrhea, or a psychiatric/social condition that may limit compliance with study requirements, cause a significantly increased risk of AEs, or interfere with the subject's ability to provide written informed consent.
- •History of another primary malignant tumor, except for the following cases;
Arms & Interventions
tislelizumab combined with bevacizumab and platinum plus pemetrexed
Drug: Induction Phase: Bevacizumab: 7.5 mg/kg administered as an IV infusion on Day 1 of each 3-week cycle for 4 cycles Cisplatin 75 mg/m2 will be administered as an intravenous infusion over 2 hours every 3 weeks for 4 cycles. Pemetrexed, 500 mg/m2, intravenously, every 3 weeks for 4 cycles Maintenance phase: Tislelizumab, 200 mg IV every 3 weeks;until disease progression or intolerance Bevacizumab: 7.5 mg/kg administered as an intravenous infusion on Day 1 of each 3-week cycle;until disease progression or intolerance
Intervention: Tislelizumab Combined With Bevacizumab and Platinum Plus Pemetrexed
Outcomes
Primary Outcomes
middle progression free survival
Time Frame: Estimated about 6 months
To evaluate the median progression-free survival (middle) of tislelizumab combined with bevacizumab and platinum-based pemetrexed in treatment-naïve advanced non-small cell lung cancer patients with sensitive EGFR mutations and high PD-L1 expression. progression free survival (mPFS)