Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGAtezolizumab
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).
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 152 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 85 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Non-Compliance | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Symptomatic Deterioration | 1 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | Atezolizumab |
|---|---|
| Age, Continuous | 68.7 Years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 147 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 135 Participants |
| Sex: Female, Male Female | 69 Participants |
| Sex: Female, Male Male | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 85 / 152 |
| other Total, other adverse events | 146 / 152 |
| serious Total, serious adverse events | 81 / 152 |
Outcome results
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.
Time frame: Baseline up to 32 months
Population: Efficacy and Safety analysis Population included participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Determined by Investigator | 17.1 Percentage of Participants |
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.
Time frame: Baseline up to 32 months
Population: Biomarker analysis population included all participants who received at least one dose of study drug and whose tumor samples had a maximum somatic allele frequency (MSAF) \>= 1%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator, by Positive Versus Negative bTMB Groups | 3.55 Months |
| bTMB High (>=16) | Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator, by Positive Versus Negative bTMB Groups | 4.98 Months |
p-value: 0.350290% CI: [0.54, 1.18]Log Rank
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.
Time frame: Baseline up to 32 months
Population: Efficacy Evaluable Population included all participants who received at least one dose of atezolizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Disease Control Rate (DCR) Per RECIST v1.1 as Determined by Investigator | 32.9 Percentage |
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.
Time frame: Baseline up to 32 months
Population: Duration of response included a subset of participants who achieved an objective response in the efficacy evaluable population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Duration of Response (DOR) Per RECIST v1.1 as Determined by Investigator | 16.33 Months |
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.
Time frame: From baseline until death (up to 32 months)
Population: Biomarker analysis population included all participants who received at least one dose of study drug and whose tumor samples had a maximum somatic allele frequency (MSAF) \>= 1%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | OS by Various bTMB Cutoff Points 16 and 20 | 13.37 Months |
| bTMB High (>=16) | OS by Various bTMB Cutoff Points 16 and 20 | 23.85 Months |
| bTMB <16 | OS by Various bTMB Cutoff Points 16 and 20 | 13.14 Months |
| bTMB >=16 | OS by Various bTMB Cutoff Points 16 and 20 | 23.85 Months |
p-value: 0.178390% CI: [0.4, 1.1]Log Rank
p-value: 0.035890% CI: [0.23, 0.85]Log Rank
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.
Time frame: From baseline until death (up to 32 months)
Population: Efficacy Evaluable Population included all participants who received at least one dose of atezolizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | Overall Survival (OS) | 14.82 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.
Time frame: Months 6, 9, 12, and 18
Population: Biomarker analysis population included all participants who received at least one dose of study drug and whose tumor samples had a maximum somatic allele frequency (MSAF) \>=1%.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atezolizumab | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 9 Months | 23.19 Percentage of Participants |
| Atezolizumab | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 6 Months | 35.67 Percentage of Participants |
| Atezolizumab | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 18 Months | 14.45 Percentage of Participants |
| Atezolizumab | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 12 Months | 16.86 Percentage of Participants |
| bTMB High (>=16) | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 18 Months | 8.16 Percentage of Participants |
| bTMB High (>=16) | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 9 Months | 22.45 Percentage of Participants |
| bTMB High (>=16) | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 12 Months | 14.29 Percentage of Participants |
| bTMB High (>=16) | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 6 Months | 34.69 Percentage of Participants |
| bTMB <16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 9 Months | 16.90 Percentage of Participants |
| bTMB <16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 6 Months | 32.85 Percentage of Participants |
| bTMB <16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 12 Months | 12.29 Percentage of Participants |
| bTMB <16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 18 Months | 10.53 Percentage of Participants |
| bTMB >=16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 18 Months | 14.29 Percentage of Participants |
| bTMB >=16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 12 Months | 25.00 Percentage of Participants |
| bTMB >=16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 6 Months | 42.86 Percentage of Participants |
| bTMB >=16 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 9 Months | 39.29 Percentage of Participants |
| bTMB <20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 12 Months | 12.24 Percentage of Participants |
| bTMB <20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 9 Months | 17.58 Percentage of Participants |
| bTMB <20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 18 Months | 9.33 Percentage of Participants |
| bTMB <20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 6 Months | 31.91 Percentage of Participants |
| bTMB >=20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 9 Months | 47.37 Percentage of Participants |
| bTMB >=20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 12 Months | 31.58 Percentage of Participants |
| bTMB >=20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 18 Months | 21.05 Percentage of Participants |
| bTMB >=20 | Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles | 6 Months | 52.63 Percentage of Participants |
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.
Time frame: Baseline up to 32 months
Population: Safety analyses population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Percentage of Participants With Adverse Events | 100 Percentage of Participants |
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.
Time frame: Baseline up to 32 months
Population: Biomarker analysis population included all participants who received at least one dose of study drug and whose tumor samples had a maximum somatic allele frequency (MSAF) \>=1%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles | 7.1 Percentage of Participants |
| bTMB High (>=16) | Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles | 20.4 Percentage of Participants |
| bTMB <16 | Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles | 5.5 Percentage of Participants |
| bTMB >=16 | Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles | 35.7 Percentage of Participants |
| bTMB <20 | Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles | 6.0 Percentage of Participants |
| bTMB >=20 | Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles | 47.4 Percentage of Participants |
p-value: 0.032690% CI: [2.53, 24]Cochran-Mantel-Haenszel
p-value: <0.000190% CI: [14.82, 45.62]Cochran-Mantel-Haenszel
p-value: <0.000190% CI: [22.13, 60.61]Cochran-Mantel-Haenszel
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.
Time frame: Baseline up to 32 months
Population: Efficacy Evaluable Population included all participants who received at least one dose of atezolizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator | 4.14 Months |