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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Atezolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atezolizumab<br>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). | Drug: Atezolizumab<br>* 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).<br>* Other names: MPDL3280A; RO5541267; Tecentriq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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 | 
| 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 | 
| 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) | 
| 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 |