Back to resultsA Study of Atezolizumab as First-line Monotherapy for Advanced or Metastatic Non-Small Cell Lung Cancer (B-F1RST)
Primary Purpose
Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Atezolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically or cytologically confirmed Stage IIIB-IVB NSCLC
- For participants who have received prior neo-adjuvant/adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease: a treatment-free interval of at least 6 months prior to enrollment
- Participants with any programmed death-ligand 1 (PD-L1) test result by immunohistochemistry (IHC) are eligible for the study
- Participants without a PD-L1 test result are eligible for the study
- Measurable disease per RECIST v1.1
- Adequate hematologic and end-organ function
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods among women of childbearing potential
Exclusion Criteria:
- Prior treatment with immunotherapy for any stage NSCLC, including early-stage (neoadjuvant or adjuvant) disease
- Participants with epidermal growth factor receptor (EGFR) sensitizing mutations and anaplastic lymphoma kinase (ALK) rearrangements
- Active central nervous system (CNS) metastases requiring treatment
- Spinal cord compression not definitively treated or not clinically stable
- Leptomeningeal disease
- Uncontrolled tumor-related pain
- Uncontrolled pleural, pericardial effusions, or ascites requiring recurrent drainage procedures
- Uncontrolled or symptomatic hypercalcemia
- Malignancies other than NSCLC within 5 years prior to enrollment, except for those curatively treated with negligible risk of metastasis or death
- Pregnant or lactating women
- History of autoimmune disease, significant pulmonary disease, or significant cardiovascular disease
- Positive human immunodeficiency virus (HIV) or hepatitis B or C
- Active tuberculosis
- Severe infection or major surgery within 4 weeks, or oral or IV antibiotics treatment within 2 weeks prior to enrollment
- Prior treatment with or hypersensitivity to study drug or related compounds
- Prior allogeneic bone marrow or solid organ transplant
- Administration of a live, attenuated vaccine within 4 weeks prior to enrollment
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to enrollment
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to enrollment
Sites / Locations
- Veterans Affairs Central California Health Care System
- Memorial Regional Hospital
- Florida Hospital
- St. Alexius Medical Center
- Quincy Medical Group; Canc Ctr at Blessing Hosp
- Franciscan St. Francis Health; Research Services
- Cancer Center of Kansas
- Michigan Cancer Rsch Cons
- Virginia Piper Cancer Inst
- San Juan Oncology Associates
- Eastchester Center for Cancer Care
- Stony Brook University Medical Center
- Levine Cancer Institute-Carolinas Medical Center; Levine Cancer Institute-Carolinas Medical Center
- The Cleveland Clinic Foundation
- Cancer Treatment Centers of America - Eastern Regional Medical Center
- Avera Research Institute
- Univ of Texas SW Medical Ctr
- Inova Health Care Services
- Western WA Oncology Inc PS
- University of Wisconsin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Atezolizumab
Arm Description
Participants received 1200 milligrams (mg) of atezolizumab administered by intravenous infusion every 21 days until disease progression, loss of clinical benefit, or unacceptable toxicity (up to a total of 2 years of atezolizumab treatment).
Outcomes
Primary Outcome Measures
Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Determined by Investigator
Investigator-assessed objective response rate was defined as the proportion of participants who had a confirmed best overall response of either PR or CR per RECIST v1.1.
Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator, by Positive Versus Negative bTMB Groups
Investigator-assessed PFS by RECIST v1.1 was defined as the time from the first dose of study drug to the time of PD or death from any cause during the study, whichever occurred first.
Secondary Outcome Measures
Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator
Investigator-assessed PFS by RECIST v1.1 was defined as the time from the first dose of study drug to the time of PD or death from any cause during the study, whichever occurred first.
Duration of Response (DOR) Per RECIST v1.1 as Determined by Investigator
Investigator-assessed DOR by RECIST v1.1 was defined as the time from initial occurrence of documented CR or PR until documented disease progression as determined by the investigator, or death, whichever occurred first.
Disease Control Rate (DCR) Per RECIST v1.1 as Determined by Investigator
Confirmed disease control rate (cDCR) was defined as the rate of patients with CR or PR as the best response, or SD maintained for 24 weeks, per RECIST v1.1.
Overall Survival (OS)
OS was defined as the time from the first dose of study drug to the time of death from any cause during the study.
Percentage of Participants With Adverse Events
Adverse events were defined as any untoward medical occurrence in a subject administered atezolizumab, regardless of causal attribution.
Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles
A summary of the number of patients at risk and survival rate for the time points of 6, 9, 12, and 18 months.
OS by Various bTMB Cutoff Points 16 and 20
OS was defined as the time from the first dose of study drug to the time of death from any cause during the study.
Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles
Objective response rate was defined as the proportion of participants who had a confirmed best overall response of either PR or CR per RECIST v1.1.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02848651
Brief Title
A Study of Atezolizumab as First-line Monotherapy for Advanced or Metastatic Non-Small Cell Lung Cancer
Acronym
B-F1RST
Official Title
A Phase II Single-Arm Study of Atezolizumab Monotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Clinical Evaluation of Novel Blood-Based Diagnostics
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
September 23, 2016 (Actual)
Primary Completion Date
May 14, 2019 (Actual)
Study Completion Date
May 14, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
This was a Phase II, open-label, prospective, multicenter study designed to evaluate the efficacy and safety of single-agent atezolizumab as a first-line therapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC). In addition, the primary biomarker objective was to measure blood tumor mutational burden (bTMB) and evaluate whether it can predict for improved clinical outcome with atezolizumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
153 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Atezolizumab
Arm Type
Experimental
Arm Description
Participants received 1200 milligrams (mg) of atezolizumab administered by intravenous infusion every 21 days until disease progression, loss of clinical benefit, or unacceptable toxicity (up to a total of 2 years of atezolizumab treatment).
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
MPDL3280A; RO5541267; Tecentriq
Intervention Description
Atezolizumab 1200 mg was administered by intravenous infusion on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity (up to a total of 2 years of atezolizumab treatment).
Primary Outcome Measure Information:
Title
Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Determined by Investigator
Description
Investigator-assessed objective response rate was defined as the proportion of participants who had a confirmed best overall response of either PR or CR per RECIST v1.1.
Time Frame
Baseline up to 32 months
Title
Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator, by Positive Versus Negative bTMB Groups
Description
Investigator-assessed PFS by RECIST v1.1 was defined as the time from the first dose of study drug to the time of PD or death from any cause during the study, whichever occurred first.
Time Frame
Baseline up to 32 months
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator
Description
Investigator-assessed PFS by RECIST v1.1 was defined as the time from the first dose of study drug to the time of PD or death from any cause during the study, whichever occurred first.
Time Frame
Baseline up to 32 months
Title
Duration of Response (DOR) Per RECIST v1.1 as Determined by Investigator
Description
Investigator-assessed DOR by RECIST v1.1 was defined as the time from initial occurrence of documented CR or PR until documented disease progression as determined by the investigator, or death, whichever occurred first.
Time Frame
Baseline up to 32 months
Title
Disease Control Rate (DCR) Per RECIST v1.1 as Determined by Investigator
Description
Confirmed disease control rate (cDCR) was defined as the rate of patients with CR or PR as the best response, or SD maintained for 24 weeks, per RECIST v1.1.
Time Frame
Baseline up to 32 months
Title
Overall Survival (OS)
Description
OS was defined as the time from the first dose of study drug to the time of death from any cause during the study.
Time Frame
From baseline until death (up to 32 months)
Title
Percentage of Participants With Adverse Events
Description
Adverse events were defined as any untoward medical occurrence in a subject administered atezolizumab, regardless of causal attribution.
Time Frame
Baseline up to 32 months
Title
Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles
Description
A summary of the number of patients at risk and survival rate for the time points of 6, 9, 12, and 18 months.
Time Frame
Months 6, 9, 12, and 18
Title
OS by Various bTMB Cutoff Points 16 and 20
Description
OS was defined as the time from the first dose of study drug to the time of death from any cause during the study.
Time Frame
From baseline until death (up to 32 months)
Title
Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles
Description
Objective response rate was defined as the proportion of participants who had a confirmed best overall response of either PR or CR per RECIST v1.1.
Time Frame
Baseline up to 32 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Histologically or cytologically confirmed Stage IIIB-IVB NSCLC
For participants who have received prior neo-adjuvant/adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease: a treatment-free interval of at least 6 months prior to enrollment
Participants with any programmed death-ligand 1 (PD-L1) test result by immunohistochemistry (IHC) are eligible for the study
Participants without a PD-L1 test result are eligible for the study
Measurable disease per RECIST v1.1
Adequate hematologic and end-organ function
Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods among women of childbearing potential
Exclusion Criteria:
Prior treatment with immunotherapy for any stage NSCLC, including early-stage (neoadjuvant or adjuvant) disease
Participants with epidermal growth factor receptor (EGFR) sensitizing mutations and anaplastic lymphoma kinase (ALK) rearrangements
Active central nervous system (CNS) metastases requiring treatment
Spinal cord compression not definitively treated or not clinically stable
Leptomeningeal disease
Uncontrolled tumor-related pain
Uncontrolled pleural, pericardial effusions, or ascites requiring recurrent drainage procedures
Uncontrolled or symptomatic hypercalcemia
Malignancies other than NSCLC within 5 years prior to enrollment, except for those curatively treated with negligible risk of metastasis or death
Pregnant or lactating women
History of autoimmune disease, significant pulmonary disease, or significant cardiovascular disease
Positive human immunodeficiency virus (HIV) or hepatitis B or C
Active tuberculosis
Severe infection or major surgery within 4 weeks, or oral or IV antibiotics treatment within 2 weeks prior to enrollment
Prior treatment with or hypersensitivity to study drug or related compounds
Prior allogeneic bone marrow or solid organ transplant
Administration of a live, attenuated vaccine within 4 weeks prior to enrollment
Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to enrollment
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Veterans Affairs Central California Health Care System
City
Fresno
State/Province
California
ZIP/Postal Code
93703
Country
United States
Facility Name
Memorial Regional Hospital
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Florida Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
St. Alexius Medical Center
City
Hoffman Estates
State/Province
Illinois
ZIP/Postal Code
60169
Country
United States
Facility Name
Quincy Medical Group; Canc Ctr at Blessing Hosp
City
Quincy
State/Province
Illinois
ZIP/Postal Code
62301
Country
United States
Facility Name
Franciscan St. Francis Health; Research Services
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Michigan Cancer Rsch Cons
City
Ypsilanti
State/Province
Michigan
ZIP/Postal Code
48197
Country
United States
Facility Name
Virginia Piper Cancer Inst
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
San Juan Oncology Associates
City
Farmington
State/Province
New Mexico
ZIP/Postal Code
87401
Country
United States
Facility Name
Eastchester Center for Cancer Care
City
Bronx
State/Province
New York
ZIP/Postal Code
10469
Country
United States
Facility Name
Stony Brook University Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Levine Cancer Institute-Carolinas Medical Center; Levine Cancer Institute-Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Cancer Treatment Centers of America - Eastern Regional Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19124
Country
United States
Facility Name
Avera Research Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
Univ of Texas SW Medical Ctr
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Inova Health Care Services
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Western WA Oncology Inc PS
City
Lacey
State/Province
Washington
ZIP/Postal Code
98503
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35422531
Citation
Kim ES, Velcheti V, Mekhail T, Yun C, Shagan SM, Hu S, Chae YK, Leal TA, Dowell JE, Tsai ML, Dakhil CSR, Stella P, Jin Y, Shames DS, Schleifman E, Fabrizio DA, Phan S, Socinski MA. Blood-based tumor mutational burden as a biomarker for atezolizumab in non-small cell lung cancer: the phase 2 B-F1RST trial. Nat Med. 2022 May;28(5):939-945. doi: 10.1038/s41591-022-01754-x. Epub 2022 Apr 14.
Results Reference
derived
Learn more about this trial
A Study of Atezolizumab as First-line Monotherapy for Advanced or Metastatic Non-Small Cell Lung Cancer
We'll reach out to this number within 24 hrs