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]

A Phase II, Multicenter, Single-arm Study of MPDL3280A in Patients With PD-L1-Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• France
  • Lyon, France, 69008
    • Centre Leon Berard
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Antoni van Leeuwenhoek Ziekenhuis
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital - Fulham; Oncology Department
  • London, United Kingdom, EC1M 6BQ
    • Queen Mary University of London
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital - Fulham
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute - Pima Center
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University/Lucile Packard Children's Hospital
    • Santa Monica, California, United States, 90025
      • The Angeles Clinic and Research Institute, Santa Monica Office
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Inst
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists.
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Inst.
  • Georgia
    • Carrollton, Georgia, United States, 30117
      • Northwest Georgia Oncology Centers P.C.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Med Center; Norris Cotton Cancer Ctr
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health Systems
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute; Can Therapy & Res Ctr
  • Ohio
    • Columbus, Ohio, United States, 43210-1250
      • Ohio State Uni Hospital
    • Hamilton, Ohio, United States, 45103
      • Oncology Hematology Care, Inc.
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Univ. Milton S. Hershey Medical Center; MSHMC Cardiology
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center; Abramson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI-Tennessee Oncology
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute; University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Virginia Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)	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 since 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.	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response According to RECIST Version 1.1 (v1.1)	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.	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 According to RECIST v1.1	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.	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)
Percentage of Participants With 6-Month Duration of Objective Response	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.	Month 6
Percentage of Participants With Disease Progression or Death According to RECIST v1.1	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.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
Progression-Free Survival (PFS) According to RECIST v1.1	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.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
Percentage of Participants With PFS at Month 6, Month 12 and Month 30 According to RECIST v1.1	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.	Months 6, 12 and 30
Percentage of Participants With Disease Progression or Death 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.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
PFS According to Modified RECIST	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.	Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)
Percentage of Participants With PFS at Month 6, Month 12 and Month 30 According to Modified RECIST	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.	Months 6, 12 and 30
Percentage of Participants With Death	Participants were followed for survival throughout the study.	Baseline till death or up to 20 months, whichever occurred first
Overall Survival (OS)	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.	Baseline till death or up to 20 months, whichever occurred first
Maximum Plasma Concentration (Cmax) for Atezolizumab		Pre-dose (0 hour) and 30 minutes after infusion on Day 1 of Cycle 1
Minimum Plasma Concentration (Cmin) for Atezolizumab		Pre-dose (0 hour) on Day 1 of Cycles 2, 3, 4, 8, and 16

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 30, 2013
• Primary Completion (ACTUAL): January 7, 2015
• Study Completion (ACTUAL): December 18, 2017

Study Registration Dates

• First Submitted: May 1, 2013
• First Submitted That Met QC Criteria: May 1, 2013
• First Posted (ESTIMATE): May 3, 2013

Study Record Updates

• Last Update Posted (ACTUAL): January 8, 2019
• Last Update Submitted That Met QC Criteria: December 14, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Atezolizumab
• Other Study ID Numbers: GO28625; 2013-000177-69 (EUDRACT_NUMBER)