Phase II Randomized Trial of Atezolizumab Versus Atezolizumab Plus Bevacizumab in PD-L1 High Advanced Non-Small-Cell Lung Cancer
- Trial ID
- 2024-517200-10-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase II randomized trial is to evaluate whether the combination of **atezolizumab** and **bevacizumab** enhances overall survival (OS) compared to **atezolizumab** alone in patients with untreated PD-L1 high metastatic **non-small-cell lung cancer** (NSCLC). This is clinically relevant as improving OS in this patient population could significantly impact treatment strategies and patient outcomes. No secondary objectives are specified for this study.
Participants
The clinical trial involves participants diagnosed with **advanced non-small-cell lung cancer**. The study population includes both male and female subjects, with an age range of 18 years and older. Participants are required to have a histologically confirmed diagnosis of stage IV non-squamous NSCLC, with no evidence of EGFR sensitizing mutations or ALK or ROS1 rearrangements. The trial does not include a vulnerable population. Participants must have a life expectancy greater than three months and an ECOG performance status of 0-1, indicating they are in relatively good health despite their condition. The trial population was selected based on specific inclusion criteria, such as high levels of PD-L1 expression and adequate hematologic and organ function. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **Phase II randomized** study designed to evaluate the efficacy of **atezolizumab** alone versus a combination of **atezolizumab** and **bevacizumab** in patients with **advanced non-small-cell lung cancer** (NSCLC) exhibiting high levels of PD-L1 expression. The primary objective is to assess whether the combination therapy improves overall survival compared to monotherapy. The trial employs a **double-blind, controlled** design to ensure unbiased results. The estimated duration of the trial is from February 2020 to December 2025, with a maximum treatment period of 12 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as histologically confirmed stage IV non-squamous NSCLC, high PD-L1 expression, and adequate organ function. Following randomization, participants will receive treatment via **intravenous infusion** and attend regular follow-up visits to monitor safety, efficacy, and any adverse events. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
The expected length of participant involvement is up to 12 months, contingent upon individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include significant adverse reactions, disease progression, or withdrawal of consent. Participants must comply with trial procedures and provide written informed consent to participate. The trial aims to provide valuable insights into the potential benefits of combination therapy in improving survival outcomes for patients with advanced NSCLC.
Treatment
The clinical trial involves the administration of two experimental medications: **bevacizumab** and **atezolizumab**. **Bevacizumab** is provided under the brand name Avastin, formulated as a 25 mg/ml concentrate for solution for infusion. It is administered intravenously. The maximum daily dose is 25 mg/ml, with a total dose not exceeding 15 mg/kg. The treatment period is capped at 12 months. **Bevacizumab** is a protein-based therapeutic agent, specifically classified under the ATC code L01FG01. The pharmaceutical form is a solution for infusion, and it is manufactured by Roche Registration GmbH.
**Atezolizumab** is supplied as Tecentriq, a 1,200 mg concentrate for solution for infusion. It is also administered via intravenous infusion. The maximum daily dose is 60 mg/ml, with a total dose limit of 1,200 mg. The treatment duration is similarly restricted to 12 months. **Atezolizumab** is a protein-based therapeutic agent, categorized under the ATC code L01FF05. The pharmaceutical form is a solution for infusion, and it is produced by Roche Registration GmbH. Both medications are not formulated for pediatric use and are not classified as orphan drugs.
In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed treatment regimen. The primary objective of the trial is to evaluate the efficacy of the combination of **atezolizumab** and **bevacizumab** in improving overall survival in patients with PD-L1 high advanced non-small-cell lung cancer, compared to **atezolizumab** alone.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the **Overall Survival (OS)** in patients with advanced non-small-cell lung cancer (NSCLC) who are treated with atezolizumab alone versus a combination of atezolizumab and bevacizumab. The primary endpoint is the comparison of OS between these two treatment groups. The trial is designed to determine if the combination therapy improves OS over the monotherapy in untreated patients with high levels of PD-L1 expression.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Histologically confirmed diagnosis of stage IV non-squamous NSCLC with no evidence of EGFR sensitizing mutations or ALK or ROS1 rearrangements. 2) Availability of tumor tissue. 3) 3) Evidence of high levels of PD-L1 expression evaluated with immunohistochemistry (=50% by 22C3 or SP263 or TC/IC 3 scoring by SP 142) . 4) 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. 5) ECOG performance status 0-1. 6) Life expectancy > 3 months 7) Age =18 years. 8) Measurable disease, as defined by RECIST v1.1. 9) Adequate hematologic and organ function, defined by the following laboratory results obtained within 28 days prior to randomization: o ANC = 1500 cells/µL without granulocyte colony-stimulating factor support o Platelet count = 100,000/µL without transfusion o Hemoglobin = 9.0 g/dL Patients may be transfused to meet this criterion o AST, ALT, and alkaline phosphatase = 2.5 × ULN, with the following exceptions: ¿ Patients with documented liver metastases: AST and/or ALT = 5 × ULN ¿ Patients with documented liver or bone metastases: alkaline phosphatase = 5 × ULN. o Serum bilirubin = 1.25 × ULN o Patients with known Gilbert disease who have serum bilirubin level = 3 mg/dL may be enrolled o Calculated creatinine clearance (CRCL) = 45 mL/min or calculated CRCL must be = 60 mL/min 10) Patient compliance to trial procedures. 11) Written informed consent.
Exclusion Criteria
- No tumor tissue available. 2. PD-L1 expression < 50 % or PD-L1 expression unknown or not assessable 3. Patient positive for EGFR mutations or ALK or ROS1 rearrangements. 4. Patients with squamous histology or with specific contraindication to bevacizumab therapy. 5. Previously treated with chemotherapy 6. Concomitant radiotherapy or chemotherapy. 7. Previous therapy with any checkpoint inhibitor. 8. Pregnancy or lactating women who are pregnant, lactating, or intending to become pregnant during the study. 9. Symptomatic brain metastases 10. Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression 11. Leptomeningeal disease. 12. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures 13. Uncontrolled or symptomatic hypercalcemia 14. Malignancies other than NSCLC within 5 years prior to randomization 15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 16. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells 17. History of autoimmune disease 18. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. 19. Positive test for HIV 20. Patients with active hepatitis B or hepatitis C. 21. Active tuberculosis 22. Severe infections within 4 weeks prior to randomization 23. Significant cardiovascular disease 24. Major surgical procedure other than for diagnosis within 28 days prior to randomization 25. Prior allogeneic bone marrow transplantation or solid organ transplant 26. Administration of a live, attenuated vaccine within 4 weeks before randomization 27. metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease 28. Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment 29. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to randomization 30. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, antiPD-1, and anti-PD-L1 therapeutic antibodies 31. Treatment with systemic immunostimulatory agents 32. Treatment with systemic immunosuppressive medications 33. Patients who have received acute, low-dose, systemic immunosuppressant medications 34. The use of steroids are permitted only as inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, low-dose supplemental corticosteroids for adrenocortical insufficiencyand corticosteroids for CT pre treatment. 35. Inadequately controlled hypertension 36. Prior history of hypertensive crisis or hypertensive encephalopathy 37. Significant vascular disease 38. History of hemoptysis (= one-half teaspoon of bright red blood per episode) within 1 month prior to randomization; 39. Current or recent use of aspirin or treatment with dipyramidole, ticlopidine, clopidogrel, and clostazol 40. Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for > 2 weeks prior to randomization 41. Prophylactic anticoagulation for the patency of venous access devices is allowed 42. Prophylactic use of low-molecular-weight heparin 43. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, 44. History of abdominal or tracheosphageal fistula or gastrointestinal perforation 45. Serious, non-healing wound, active ulcer, or untreated bone fracture 46. Proteinuria 47. Known sensitivity to any component of bevacizumab E.5 - End Points
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 25 Feb 2020 | 130 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Avastin 25 mg/ml concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 25 | 12 | PRD2153901 |
Tecentriq 1 200 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 60 | 12 | PRD5434939 |