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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 : November 26, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Atezolizumab Drug: Bevacizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 9, 2020
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Incidence of Adverse Events [ Time Frame: Baseline up to approximately 3 years ]
  9. 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.

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04426825


Contacts
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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

Locations
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China
Beijing Cancer Hospital Recruiting
Beijing, China, 100142
Beijing Hospital; Internal Medicine-Oncology Recruiting
Beijing, China, 100730
Beijing Chest Hospital; Oncology Department Recruiting
Beijing, China, 101149
the First Hospital of Jilin University; Cancer Center Not yet recruiting
Changchun, China
West China Hospital, Sichuan University Recruiting
Chengdu, China, 610041
Cancer Center of Guangzhou Medical University Not yet recruiting
Guangzhou, China, 510000
Sun Yet-sen University Cancer Center Recruiting
Guangzhou, China, 510060
Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department Recruiting
Hangzhou, China, 310022
Harbin Medical University Cancer Hospital Recruiting
Harbin, China, 150081
Shandong Cancer Hospital Recruiting
Jinan, China, 250117
Guangxi Cancer Hospital of Guangxi Medical University Recruiting
Nanning, China, 530021
The Affiliated Hospital of Medical College Qingdao University Recruiting
Qingdao, China, 266000
Fudan University Shanghai Cancer Center; Medical Oncology Not yet recruiting
Shanghai, China, 200032
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04426825    
Other Study ID Numbers: ML41256
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: November 26, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
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).

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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
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors