A Study of Atezolizumab as First-line Monotherapy for Advanced or Metastatic Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02848651
• Other study ID #: ML39237
• Status: Completed
• Phase: Phase 2
• Start date: September 23, 2016
• Est. completion date: May 14, 2019

Study information

• Verified date: April 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: May 14, 2019
• Est. primary completion date: May 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Atezolizumab
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).

Locations

Country	Name	City	State
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Levine Cancer Institute-Carolinas Medical Center; Levine Cancer Institute-Carolinas Medical Center	Charlotte	North Carolina
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Univ of Texas SW Medical Ctr	Dallas	Texas
United States	Inova Health Care Services	Falls Church	Virginia
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Veterans Affairs Central California Health Care System	Fresno	California
United States	St. Alexius Medical Center	Hoffman Estates	Illinois
United States	Memorial Regional Hospital	Hollywood	Florida
United States	Franciscan St. Francis Health; Research Services	Indianapolis	Indiana
United States	Western WA Oncology Inc PS	Lacey	Washington
United States	University of Wisconsin	Madison	Wisconsin
United States	Virginia Piper Cancer Inst	Minneapolis	Minnesota
United States	Florida Hospital	Orlando	Florida
United States	Cancer Treatment Centers of America - Eastern Regional Medical Center	Philadelphia	Pennsylvania
United States	Quincy Medical Group; Canc Ctr at Blessing Hosp	Quincy	Illinois
United States	Avera Research Institute	Sioux Falls	South Dakota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Michigan Cancer Rsch Cons	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to 32 months
Primary	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.	Baseline up to 32 months
Secondary	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.	Baseline up to 32 months
Secondary	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.	Baseline up to 32 months
Secondary	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.	Baseline up to 32 months
Secondary	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.	From baseline until death (up to 32 months)
Secondary	Percentage of Participants With Adverse Events	Adverse events were defined as any untoward medical occurrence in a subject administered atezolizumab, regardless of causal attribution.	Baseline up to 32 months
Secondary	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.	Months 6, 9, 12, and 18
Secondary	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.	From baseline until death (up to 32 months)
Secondary	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.	Baseline up to 32 months