Clinical Trials /

A Study of Atezolizumab in Combination With Bevacizumab in Patients With EGFR Mutation Positive Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer

NCT04426825

Description:

This is an open-label, single-arm, phase II, multicenter study designed to evaluated the efficacy and safety of atezolizumab in combination with bevacizumab in PD-L1-selected patients with Stage IIIB/IV Non-Squamous NSCLC harbored EGFR mutation after EGFR TKI therapy.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab in Combination With Bevacizumab in Patients With EGFR Mutation Positive Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer
  • Official Title: A Single Arm, Phase II Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Bevacizumab in Patients With EGFR Mutation Positive Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer Pretreated With Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitors

Clinical Trial IDs

  • ORG STUDY ID: ML41256
  • NCT ID: NCT04426825

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezolizumab plus Bevacizumab
BevacizumabAvastinAtezolizumab plus Bevacizumab

Purpose

This is an open-label, single-arm, phase II, multicenter study designed to evaluated the efficacy and safety of atezolizumab in combination with bevacizumab in PD-L1-selected patients with Stage IIIB/IV Non-Squamous NSCLC harbored EGFR mutation after EGFR TKI therapy.

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab plus BevacizumabExperimentalParticipants will receive atezolizumab plus bevacizumab intravenously on Day 1 of each cycle. Treatment will continue until progressive disease, unacceptable toxicity, or death.
  • Atezolizumab
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Life expectancy ≥ 10 months

          -  Histologically or cytologically confirmed stage IIIB or IV non-squamous NSCLC.
             Patients with tumors of mixed histology are eligible if the major histological
             component appears to be non-squamous.

          -  No prior treatment for Stage IIIB or IV non-squamous NSCLC, with the following
             exceptions:

        Patients with a sensitizing mutation in the EGFR gene must have experienced disease
        progression or were intolerant to treatment with one or more EGFR TKIs. Patients who have
        progressed on or were intolerant to first-line osimertinib or other thirdgeneration EGFR
        TKIs are eligible.

        Patients who have progressed on or were intolerant to first- or second-generation EGFR
        TKIs, and who have no evidence of the EGFR T790M mutation after TKI therapy are eligible.

        Patients who have progressed on or were intolerant to first- or second-generation EGFR TKIs
        and who have evidence of the T790M mutation must have also progressed on or were intolerant
        to osimertinib to be eligible.

          -  TKIs approved for treatment of NSCLC discontinued >7 days prior to enrollment.

          -  Measurable disease per RECIST v1.1. PD-L1 expression of ≥1% as documented through
             central testing of a representative tumor tissue specimen either from previously
             obtained archival tumor tissue or tissue obtained from a biopsy at screening

          -  ECOG Performance Status of 0-1

          -  Adequate hematologic and end-organ function

          -  Negative HIV test at screening

          -  Negative hepatitis B surface antigen (HBsAg) test at screening

          -  Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
             HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The
             HBV DNA test will be performed only for patients who have a positive total HBcAb test.

          -  Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
             test followed by a negative HCV RNA test at screening. The HCV RNA test will be
             performed only for patients who have a positive HCV antibody test.

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods, and agreement to refrain from
             donating eggs.

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             a condom, and agreement to refrain from donating sperm.

        Exclusion Criteria:

          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)
             metastases as determined by CT or MRI evaluation during screening and prior
             radiographic assessments

          -  History of leptomeningeal disease

          -  Prior chemotherapy or other systemic therapy for stage IIIB/IV disease

          -  Active or history of autoimmune disease or immune deficiency

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest computed tomography (CT) scan

          -  Active tuberculosis

          -  Significant cardiovascular disease within 3 months prior to initiation of study
             treatment, unstable arrhythmia, or unstable angina

          -  History of malignancy other than NSCLC within 5 years prior to screening, with the
             exception of malignancies with a negligible risk of metastasis or death

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
             treatment, or anticipation of need for such a vaccine during atezolizumab treatment or
             within 5 months after the final dose of atezolizumab

          -  Current treatment with anti-viral therapy for HBV

          -  Treatment with investigational therapy within 28 days prior to initiation of study
             treatment

          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies

          -  Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the
             drug (whichever is longer) prior to initiation of study treatment

          -  Treatment with systemic immunosuppressive medication within 2 weeks prior to
             initiation of study treatment, or anticipation of need for systemic immunosuppressive
             medication during study treatment

          -  History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
             or fusion proteins

          -  Known hypersensitivity to Chinese hamster ovary cell products or to any component of
             the atezolizumab or bevacizumab formulations

          -  Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
             or within 5 months after the final dose of atezolizumab, 6 months after the final dose
             of bevacizumab

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  Significant vascular disease within 6 months prior to initiation of study treatment

          -  History of Grade ≥ 2 hemoptysis within 1 month prior to enrollment

          -  Evidence of bleeding diathesis or coagulopathy. Current or recent use of aspirin,
             clopidogrel or treatment with dipyramidole, ticlopidine, or cilostazol

          -  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 enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to enrollment

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to the first dose of bevacizumab

          -  History of abdominal or tracheosphageal fistula or gastrointestinal perforation within
             6 months prior to enrollment

          -  History of intra-abdominal inflammatory process within 6 months prior to initiation of
             study treatment, including but not limited to active peptic ulcer disease,
             diverticulitis,or colitis

          -  Clinical signs of gastrointestinal obstruction or requirement for routine parenteral
             hydration, parenteral nutrition, or tube feeding

          -  Evidence of abdominal free air not explained by paracentesis or recent surgical
             procedure

          -  Proteinuria

          -  Clear tumor infiltration into the thoracic great vessels is seen on imaging

          -  Clear cavitation of pulmonary lesions is seen on imaging
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) Rate at 6 Months
Time Frame:6 months
Safety Issue:
Description:PFS rate at 6 months, defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months after enrollment, as determined by the investigator according to RECIST v1.1

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:Objective response rate (ORR), defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to RECIST v1.1
Measure:Duration of Objective Response (DOR)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:Duration of objective response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause whichever occurs first, as determined by the investigator according to RECIST v1.1.
Measure:Time to Response (TTR)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:Time to response (TTR), defined as the time from the start of the treatment to the first objective tumor response observed for patients who achieved CR or PR, as determined by the investigator according to RECIST v1.1.
Measure:Overall Survival (OS)
Time Frame:Baseline until death due to any cause (up to approximately 3 years)
Safety Issue:
Description:Overall survival (OS) after enrollment, defined as the time from enrollment to death from any cause.
Measure:Progression-Free Survival (PFS)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:Progression-free survival (PFS), defined as the time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1
Measure:PFS Rate at 12 Months
Time Frame:12 months
Safety Issue:
Description:PFS rate at 12 months, defined as the proportion of patients who have not experienced disease progression or death from any cause at 12 months, as determined by the investigator according to RECIST v1.1.
Measure:OS Rate at 1 and 2 Years
Time Frame:1 and 2 Years
Safety Issue:
Description:OS rate at 1 and 2 years, defined as the proportion of patients who have not experienced death from any cause at 1 and 2 years.
Measure:Incidence of Adverse Events
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Incidence of Serious and Non-Serious Immune-Related Adverse Events (irAEs)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:Incidence of serious and non-serious immune-related adverse events (irAEs) related to atezolizumab treatment.
Measure:Consistency Among in SP 142 and SP 263
Time Frame:Baseline up to approximately 12 months
Safety Issue:
Description:Participants will be tested by two kits - SP 142 and SP 263. Positive results from SP142 or SP263 will be accepted. Sp142 +/Sp263- and Sp142-/ SP263+ (cutoff data is 1% positive) data will be collected to do the consistency test by x2-test.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

June 9, 2020