Phase II Randomized Trial Comparing Atezolizumab Versus Atezolizumab Plus Bevacizumab as First-line Treatment in PD-L1+ Advanced Metastatic Non-small-cell Lung Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Non-small-cell Lung Cancer Patients
- Sponsor
- Fondazione Ricerca Traslazionale
- Enrollment
- 206
- Locations
- 33
- Primary Endpoint
- Overall Survival (OS)
- Status
- Active, Not Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
phase II controlled randomized study comparing atezolizumab as single agent to the combination of atezolizumab and bevacizumab in patients with chemonaive metastatic NSCLC with PD-L1 expression. All NSCLC patients with tumor tissue available for biomarker assessment and candidate for first-line therapy are considered eligible for the study. After evaluation of all inclusion and exclusion criteria and after informed consent signature all eligible patients will be randomized to atezolizumab (Arm A) or to the combination of atezolizumab and bevacizumab (Arm B). Disease assessment will be performed every 6 weeks.
Detailed Description
This is a phase II controlled randomized study comparing atezolizumab as single agent to the combination of atezolizumab and bevacizumab in patients with chemonaive metastatic NSCLC with PD-L1 expression. A total of maximum of 206 patients will be enrolled in the study. Patients will be treated with atezolizumab (1200 mg) every 3 weeks (6-week cycles) or the combination of atezolizumab (1200 mg) every 3 weeks (6-week cycles) plus bevacizumab (15 mg/kg) every 3 weeks until disease progression, unacceptable toxicity or patient refusal. Disease evaluation, along with various assessments, will be made every 3 weeks and every 6 weeks and follow-up every 3 months. Toxicities will be evaluated throughout the study period. A follow-up of 12 months is planned for each patient from the end of treatment .The study will be performed in approximately 20 centers across Italy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed diagnosis of stage IV non-squamous NSCLC with no evidence of EGFR sensitizing mutations or ALK or ROS1 rearrangements.
- •Availability of tumor tissue.
- •Evidence of PD-L1 expression evaluated with immunohistochemistry (≥1%).
- •No previous chemotherapy. Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy.
- •ECOG performance status 0-
- •Life expectancy \> 3 months
- •Age ≥18 years.
- •Measurable disease, as defined by RECIST v1.
- •Adequate hematologic and organ function, defined by the following laboratory results obtained within 28 days prior to randomization:
- •ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support
Exclusion Criteria
- •No tumor tissue available.
- •PD-L1 expression \< 1 % or PD-L1 expression unknown or not assessable
- •Patient positive for EGFR mutations or ALK or ROS1 rearrangements.
- •Patients with squamous histology or with specific contraindication to bevacizumab therapy.
- •Previous chemotherapy. Adjuvant or neoadjuvant chemotherapy is considered a line of therapy if completed less than 6 months before evidence of disease relapse.
- •Concomitant radiotherapy or chemotherapy.
- •Previous therapy with any checkpoint inhibitor.
- •Pregnancy or lactating women who are pregnant, lactating, or intending to become pregnant during the study.
- •Symptomatic brain metastases; asymptomatic brain metastases are accepted if no steroid therapy is required and if pretreated.
- •Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \> 2 weeks prior to randomization.
Arms & Interventions
Atezolizumab
Patients allocated to Arm A will be treated with atezolizumab administered intravenously at 1200 mg every 3 weeks given until disease progression, toxicity or patient refusal
Intervention: Atezolizumab
Atezolizumab plus bevacizumab
Patients in the Arm B will receive atezolizumab administered intravenously at 1200 mg every 3 weeks plus bevacizumab intravenously at 15 mg/kg every 3 weeks given until disease progression, toxicity or patient refusal
Intervention: Atezolizumab
Atezolizumab plus bevacizumab
Patients in the Arm B will receive atezolizumab administered intravenously at 1200 mg every 3 weeks plus bevacizumab intravenously at 15 mg/kg every 3 weeks given until disease progression, toxicity or patient refusal
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: 18 months
Overall Survival (OS) rate at 18 months in patients treated with atezolizumab alone versus atezolizumab-bevacizumab combination
Secondary Outcomes
- Response rate (complete + partial responses)(Up to 24 months)
- Progression-free survival(Up to 24 months)
- Overall survival according to presence of bone and/ or hepatic metastases(Up to 24 months)