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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04426825
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : December 23, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 9, 2020
First Posted Date  ICMJE June 11, 2020
Last Update Posted Date December 23, 2020
Actual Study Start Date  ICMJE September 9, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2020)
Progression Free Survival (PFS) Rate at 6 Months [ Time Frame: 6 months ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2020)
  • Objective Response Rate (ORR) [ Time Frame: Baseline up to approximately 3 years ]
    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
  • Duration of Objective Response (DOR) [ Time Frame: Baseline up to approximately 3 years ]
    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.
  • Time to Response (TTR) [ Time Frame: Baseline up to approximately 3 years ]
    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.
  • Overall Survival (OS) [ Time Frame: Baseline until death due to any cause (up to approximately 3 years) ]
    Overall survival (OS) after enrollment, defined as the time from enrollment to death from any cause.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to approximately 3 years ]
    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
  • PFS Rate at 12 Months [ Time Frame: 12 months ]
    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.
  • OS Rate at 1 and 2 Years [ Time Frame: 1 and 2 Years ]
    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.
  • Incidence of Adverse Events [ Time Frame: Baseline up to approximately 3 years ]
  • Incidence of Serious and Non-Serious Immune-Related Adverse Events (irAEs) [ Time Frame: Baseline up to approximately 3 years ]
    Incidence of serious and non-serious immune-related adverse events (irAEs) related to atezolizumab treatment.
  • Consistency Among in SP 142 and SP 263 [ Time Frame: Baseline up to approximately 12 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: Atezolizumab
    Atezolizumab will be administered at a dose of 1200 mg intravenously on Day 1 of each 21-day cycle.
    Other Name: Tecentriq
  • Drug: Bevacizumab
    Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
    Other Name: Avastin
Study Arms  ICMJE Experimental: Atezolizumab plus Bevacizumab
Participants will receive atezolizumab plus bevacizumab intravenously on Day 1 of each cycle. Treatment will continue until progressive disease, unacceptable toxicity, or death.
Interventions:
  • Drug: Atezolizumab
  • Drug: Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2020)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: ML41256 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04426825
Other Study ID Numbers  ICMJE ML41256
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP