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

Phase 1

• Conditions: Advanced non-small-cell lung cancer; MedDRA version: 20.0Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003973-82-IT
• Lead Sponsor: FONDAZIONE RICERCA TRASLAZIONALE (FORT)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-14
• Last Update Posted: 12 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 206

Inclusion Criteria

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:
oANC = 1500 cells/µL without granulocyte colony-stimulating factor support
oPlatelet count = 100,000/µL without transfusion
oHemoglobin = 9.0 g/dL
Patients may be transfused to meet this criterion
oAST, 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.
oSerum bilirubin = 1.25 × ULN
oPatients with known Gilbert disease who have serum bilirubin level = 3 mg/dL may be enrolled
oCalculated creatinine clearance (CRCL) = 45 mL/min or calculated CRCL must be = 60 mL/min
10)Patient compliance to trial procedures.
11)Written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 103
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 103

Exclusion Criteria

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, anti-PD-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 fo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified