Phase II randomized trial comparing atezolizumab versus atezolizumab plus bevacizumab as first-line treatment in PD-L1 high advanced non-small-cell lung cancer patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Ricerca Traslazionale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Jan 2020 → ongoing

Decision date (initial)

2024-11-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517200-10-00

EudraCT number

2018-003973-82

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess whether the combination of atezolizumab and bevacizumab improves overall survival (OS) over atezolizumab as single agent in untreated PD-L1 high metastatic NSCLC.

Conditions and MedDRA coding

Advanced non-small-cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1) 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 1

1. 1. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS) in patients treated with atezolizumab alone versus atezolizumab-bevacizumab combination

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Ricerca Traslazionale

Sponsor organisation

Fondazione Ricerca Traslazionale

Address

Via Dei Santi Quattro 61

City

Rome

Postcode

00184

Country

Italy

Scientific contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Federico Cappuzzo

Public contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Federico Cappuzzo

Locations

1 EU/EEA country · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications