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A Study of Atezolizumab in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) [FIR]

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01846416
First received: May 1, 2013
Last updated: October 24, 2016
Last verified: October 2016
  Purpose

This multicenter, single-arm study will evaluate the efficacy and safety of atezolizumab (MPDL3280A) in participants with PD-L1-positive locally advanced or metastatic NSCLC. Participants will receive an intravenous (IV) dose of 1200 milligrams (mg) atezolizumab (MPDL3280A) on Day 1 of 21-day cycles until disease progression.

Eligible participants will be categorized in to three groups as follows:

  1. Participants with no prior chemotherapy for advanced disease;
  2. Participants who progress during or following a prior-platinum based chemotherapy regimen for advanced disease (2L+participants);
  3. Participants who are 2L+ and previously treated for brain metastases.

Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Single-arm Study of MPDL3280A in Patients With PD-L1-Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months) ]
    Objective response was defined as a complete response (CR) or partial response (PR), as determined by investigator according to modified RECIST criteria. Modified RECIST was derived from RECIST v1.1 conventions and immune related response criteria. CR was defined as disappearance of all tumor lesions (target lesion [TL] and non-target lesion [non-TL]) and no new measurable or unmeasurable lesions, all lymph node short axes must be less than 10 millimeters (mm), and PR was defined as at least 30 percent (%) decrease in sum of diameter of TLs, and all new measurable lesions to baseline in absence of CR, and both confirmed by consecutive assessment greater than or equal to 4 weeks from date first documented. Participants not meeting these criteria, including participants without at least one post-baseline response assessment were considered as non-responders.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response According to RECIST Version 1.1 (v1.1) [ Time Frame: Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months) ]
    Objective response was defined as a CR or PR, as determined by the investigator according to RECIST v1.1. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must had reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of TLs, taking as reference the baseline sum of diameters, in absence of CR. For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Participants not meeting these criteria, including participants without at least 1 post-baseline response assessment were considered as non-responders.

  • Duration of Objective Response According to RECIST v1.1 [ Time Frame: Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months) ]
    Duration of objective response was defined as time from initial occurrence of documented CR or PR until documented disease progression (using RECIST v1.1 as determined by investigator) or death, whichever occurred first. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must had reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameter of TLs, taking as reference baseline sum of diameters, in absence of CR. Progressive disease was at least a 20% increase in sum of diameters of TLs, taking as reference smallest sum on study (nadir). For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Participants were censored at the date of last tumor assessment.

  • Percentage of Participants With 6-Month Duration of Objective Response [ Time Frame: Month 6 ]
    Duration of objective response at 6 months was defined as time from initial occurrence of documented CR or PR until Month 6. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameter of TLs, taking as reference baseline sum of diameters, in absence of CR. For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Participants were censored at the date of last tumor assessment.

  • Percentage of Participants With Disease Progression or Death According to RECIST v1.1 [ Time Frame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months) ]
    For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.

  • Progression-Free Survival (PFS) According to RECIST v1.1 [ Time Frame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months) ]
    PFS was defined as time from randomization to first occurrence of documented disease progression (based on RECIST v1.1 criteria) or death due to any cause within 30 days of the last treatment, whichever occurs earlier as determined by investigator. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameter of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. In event of no disease progression or documented death, PFS was censored at date of last evaluable tumor assessment. Participants with no post-baseline tumor assessments were censored at the time of first dose plus 1 day.

  • Percentage of Participants With PFS at Month 6 and Month 12 According to RECIST v1.1 [ Time Frame: Months 6 and 12 ]
    Percentage of participants who were progression free at Month 6 and 12 (based on RECIST v1.1) was reported. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameter of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.

  • Percentage of Participants With Disease Progression or Death According to Modified RECIST [ Time Frame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months) ]
    For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started.

  • PFS According to Modified RECIST [ Time Frame: Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months) ]
    PFS according to modified RECIST was defined as time from first dose of atezolizumab to first occurrence of documented disease progression or death due to any cause, as determined by investigator for participants who discontinued at first documented radiographic progression. For participants who continued beyond first documented progression and had follow-up tumor assessment or death, PFS was defined as time from first dose of atezolizumab to subsequent radiographic progression or death. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started. In event of no disease progression or documented death, PFS was censored at date of last evaluable tumor assessment.

  • Percentage of Participants With PFS at Month 6 and Month 12 According to Modified RECIST [ Time Frame: Months 6 and 12 ]
    Percentage of participants who were progression free at Months 6 and 12 (according to modified RECIST). For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started.

  • Percentage of Participants With Death [ Time Frame: Baseline till death or up to 20 months, whichever occurred first ]
    Participants were followed for survival throughout the study.

  • Overall Survival (OS) [ Time Frame: Baseline till death or up to 20 months, whichever occurred first ]
    OS was defined as the time from first dose of the study drug to the time of death from any cause of the study. Participants who were still alive at the time of analysis were censored at the time of their last study assessment (for active participants) or at the last date known alive (for participants in follow-up). If no post-baseline data were available, OS was censored at the date of first treatment plus 1 day.

  • Maximum Plasma Concentration (Cmax) for Atezolizumab [ Time Frame: Pre-dose (0 hour) and 30 minutes after infusion on Day 1 of Cycle 1 ]
  • Minimum Plasma Concentration (Cmin) for Atezolizumab [ Time Frame: Pre-dose (0 hour) on Day 1 of Cycles 2, 3, 4, 8, and 16 ]

Enrollment: 138
Study Start Date: May 2013
Estimated Study Completion Date: July 2017
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atezolizumab (MPDL3280): 1L Participants
Participants with no prior chemotherapy for advanced NSCLC disease will receive atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until disease progression.
Drug: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody
Atezolizumab 1200 mg IV on Day 1 of each 21-day cycle until disease progression.
Experimental: Atezolizumab (MPDL3280): 2L+ Participants
Participants who progress during or following a prior platinum-based chemotherapy regimen without restriction to maximum number of prior therapies will receive atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until no longer deemed to be experiencing clinical benefit as assessed by the investigator.
Drug: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody
Atezolizumab 1200 mg IV on Day 1 of each 21-day cycle until disease progression.
Experimental: Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Participants with previously treated brain metastases and who progress during or following a prior platinum-based chemotherapy regimen without restriction to the maximum number of prior therapies, will receive atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until no longer deemed to be experiencing clinical benefit as assessed by the investigator.
Drug: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody
Atezolizumab 1200 mg IV on Day 1 of each 21-day cycle until disease progression.

  Eligibility

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

Inclusion Criteria:

  • Stage IIIB (not eligible for definitive chemoradiotherapy), Stage IV, or recurrent NSCLC
  • PDL1-positive status as determined by an immunohistochemistry assay performed by a central laboratory. A positive result in chemotherapy, chemoradiation of the tumor sample biopsy will satisfy the eligibility criterion
  • Eastern Cooperative Oncology group Performance Status of 0 or 1
  • Life expectancy greater than or equal to 12 weeks
  • Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors Version 1.1
  • Adequate hematologic and end organ function

Exclusion Criteria:

  • Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exceptions are allowed. Hormone-replacement therapy or oral contraceptives, and tyrosine kinase inhibitors approved for treatment of NSCLC discontinued greater than 7 days prior to Cycle 1 Day 1
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
  • Known central nervous system disease, including treated brain metastases in the following participants:

    1. who will not receive prior chemotherapy for advanced disease
    2. who progress during or following a prior-platinum based chemotherapy regimen for advanced disease (referred as 2L+ participants)
  • Participants with a history of treated asymptomatic brain metastases are allowed in the 2L+ participants and previously treated for brain metastases.
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled hypercalcemia
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01846416

  Show 29 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01846416     History of Changes
Other Study ID Numbers: GO28625
2013-000177-69 ( EudraCT Number )
Study First Received: May 1, 2013
Results First Received: October 24, 2016
Last Updated: October 24, 2016

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 24, 2017