A Study of Atezolizumab as First-line Monotherapy for Advanced or Metastatic Non-Small Cell Lung Cancer
- Registration Number
- NCT02848651
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 153
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Atezolizumab Atezolizumab 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).
- Primary Outcome Measures
Name Time Method Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Determined by Investigator Baseline up to 32 months 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 Baseline up to 32 months 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
Name Time Method Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator Baseline up to 32 months 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 Baseline up to 32 months 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.
Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles Baseline up to 32 months 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.
Disease Control Rate (DCR) Per RECIST v1.1 as Determined by Investigator Baseline up to 32 months 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) From baseline until death (up to 32 months) 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 Baseline up to 32 months 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 Months 6, 9, 12, and 18 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 From baseline until death (up to 32 months) OS was defined as the time from the first dose of study drug to the time of death from any cause during the study.
Trial Locations
- Locations (20)
Franciscan St. Francis Health; Research Services
🇺🇸Indianapolis, Indiana, United States
Virginia Piper Cancer Inst
🇺🇸Minneapolis, Minnesota, United States
Levine Cancer Institute-Carolinas Medical Center; Levine Cancer Institute-Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Veterans Affairs Central California Health Care System
🇺🇸Fresno, California, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
St. Alexius Medical Center
🇺🇸Hoffman Estates, Illinois, United States
Quincy Medical Group; Canc Ctr at Blessing Hosp
🇺🇸Quincy, Illinois, United States
Avera Research Institute
🇺🇸Sioux Falls, South Dakota, United States
Univ of Texas SW Medical Ctr
🇺🇸Dallas, Texas, United States
Western WA Oncology Inc PS
🇺🇸Lacey, Washington, United States
Cancer Treatment Centers of America - Eastern Regional Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Michigan Cancer Rsch Cons
🇺🇸Ypsilanti, Michigan, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Eastchester Center for Cancer Care
🇺🇸Bronx, New York, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Inova Health Care Services
🇺🇸Falls Church, Virginia, United States