Non-Small Cell Lung Cancer
Conditions
Brief summary
This is a Phase III, global, multicenter, open-label, randomized study to compare the efficacy and safety of 16 cycles (1 cycle duration=21 days) of atezolizumab (MPDL3280A) treatment compared with best supportive care (BSC) in participants with Stage IB-Stage IIIA non-small cell lung cancer (NSCLC) following resection and adjuvant chemotherapy, as measured by disease-free survival (DFS) as assessed by the investigator and overall survival (OS). Participants, after completing up to 4 cycles of adjuvant cisplatin-based chemotherapy, will be randomized in a 1:1 ratio to receive atezolizumab for 16 cycles or BSC.
Interventions
DRUGAtezolizumab
Participants will receive atezolizumab (1200 mg IV) Q3W for 16 cycles (cycle length=21 days).
DRUGCisplatin
Participants will receive cisplatin 75 milligrams per square meter (mg/m\^2) IV on Day 1 of up to four 21-day cycles.
DRUGVinorelbine
Participants will receive vinorelbine 30 mg/m\^2 IV on Days 1 and 8 of each of the four 21-day cycles.
DRUGDocetaxel
Participants will receive docetaxel 75 mg/m\^2 IV on Day 1 of each of the four 21-day cycles.
DRUGGemcitabine
Participants will receive gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of each of the four 21-day cycles.
DRUGPemetrexed
Participants will receive pemetrexed 500 mg/m\^2 IV on Day 1 of each of the four 21-day cycles. Pemetrexed will be administered only in participants with non-squamous cell NSCLC.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria for Enrollment Phase * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histological or cytological diagnosis of Stage IB (tumors greater than or equal to \[\>/=\] 4 centimeters \[cm\])-IIIA (T2-3 N0, T1-3 N1, T1-3 N2, T4 N0-1) NSCLC (per the Union Internationale Contre le Cancer staging system (UICC)/American Joint Committee on Cancer staging system (AJCC) staging system, 7th edition; Detterbeck et al. 2009) * Participants must have had complete resection of NSCLC 4-12 weeks (\>/=28 days and less than or equal to \[\</=\] 84 days) prior to enrollment and must be adequately recovered from surgery * If mediastinoscopy was not performed preoperatively, it is required that, at a minimum, mediastinal lymph node systematic sampling will have occurred. Systematic sampling is defined as removal of at least one representative lymph node at specified levels. MLND entails resection of all lymph nodes at those same levels. For a right thoracotomy, sampling or MLND is required at levels 4 and 7 and for a left thoracotomy, levels 5 and/or 6 and 7. Exceptions will be granted if there is clear documentation in the operative report or in a separately submitted addendum by the surgeon of exploration of the required lymph node areas, the participant will be considered eligible if no lymph nodes are found in those areas; if participants have documented N2 disease in one level (per the UICC/AJCC staging system, 7th edition; Detterbeck et al. 2009), not all levels need to be sampled; if the preoperative staging imaging results (contrast computed tomography \[CT\] and positron emission tomography \[PET\] scans) do not suggest evidence of disease in the mediastinum, the participant will be considered eligible if N2 nodal sampling is not performed per surgeon's decision * Eligible to receive a cisplatin-based chemotherapy regimen * Adequate hematologic and end-organ function * Women who are not postmenopausal (\>/=12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of cisplatin-based chemotherapy Inclusion Criteria for Randomized Phase - Women who are not postmenopausal (\>/=12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of atezolizumab or BSC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival (DFS) in Intent-to-treat (ITT) Population | Up to 95 months | DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm. |
| DFS in All Randomized Stage II-IIIA Population | Up to 95 months | DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in participants with disease stage II-IIIA. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm. |
| DFS in the Programmed Death-ligand 1 (PD-L1) SP263 ≥ 1% Tumor Cell (TC) Subpopulation Within the Stage II-IIIA Population | Up to 95 months | DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in PD-L1 ≥1% subpopulation within the Stage II-IIIA population. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in the ITT Population | Baseline up to death from any cause (up to approximately 126 months) | OS was defined as the time from randomization to death from any cause. |
| Disease-free Rate at Year 3 in ITT Population | Year 3 | DFS rate was defined as percentage of participants who were disease-free at Year 3. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal. |
| Disease-free Rate at Year 3 in All Randomized Stage II-IIIA Population | Year 3 | DFS rate was defined as percentage of participants who were disease-free at Year 3. DFS rate was analyzed in participants with disease stage II-IIIA. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal. |
| Disease-free Rate at Year 3 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population | Year 3 | DFS rate was defined as percentage of participants who were disease-free at Year 3. DFS rate was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal. |
| Disease-free Rate at Year 5 in ITT Population | Year 5 | DFS rate was defined as percentage of participants who were disease-free at Year 5. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal. |
| Disease-free Rate at Year 5 in All Randomized Stage II-IIIA Population | Year 5 | DFS rate was defined as percentage of participants who were disease-free at Year 5. DFS rate was analyzed in participants with disease stage II-IIIA. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal. |
| Disease-free Rate at Year 5 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population | Year 5 | DFS rate was defined as percentage of participants who were disease-free at Year 5. DFS rate was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal. |
| DFS in the PD-L1 (SP263 ≥ 50% TC) Subpopulation Within the Stage II-IIIA Population | Up to 95 months | DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm. |
| Percentage of Participants With Adverse Events (AEs) | Up to 12 years | An AE is any untoward medical occurrence in a participant when administered a pharmaceutical product regardless of the causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | Predose (Hour 0) on Day 1 of Cycles 2, 3, 4, 8, 16 (Cycle length = 21 days), at treatment discontinuation (TD) (up to 12 months), 120 days after last atezolizumab administration (up to 16 months) | The percentage of ATA (Also called anti-drug antibodies (ADA))-positive participants after drug administration were determined for participants exposed to atezolizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. |
| Maximum Plasma Concentration (Cmax) of Atezolizumab | 30 min post-infusion on Day 1 of Cycle 1 (Cycle length = 21 days) | — |
| Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Prior to infusion on Day 1 of Cycles 1, 2, 3, 4, 8, 16 (Cycle length = 21 days), at study discontinuation visit (up to 12 months), Day 120 post last dose of atezolizumab (up to 16 months) | — |
Countries
Australia, Belgium, China, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Netherlands, Poland, Portugal, Romania, Russia, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 1280 participants with resectable Stage IB-IIIA non-small cell lung cancer (NSCLC) were enrolled in this study. Participants took part in the study at 227 investigative sites across 22 countries. The study is still ongoing.
Pre-assignment details
The study consists of 2 phases, an enrollment phase in which participants received up to 4 cycles of adjuvant cisplatin-based chemotherapy followed by randomized phase in which eligible participants were randomized to receive atezolizumab or best supportive care (BSC) i.e.no treatment.
Participants by arm
| Arm | Count |
|---|---|
| Enrollment Phase All participants received up to four 21-day cycles of cisplatin-based chemotherapy (cisplatin plus either vinorelbine or docetaxel or gemcitabine or pemetrexed \[non-squamous cell NSCLC only\] based on investigator's choice), unless unacceptable toxicity, disease relapse, or participant's decision to discontinue occurred. | 1,280 |
| Total | 1,280 |
Baseline characteristics
| Characteristic | Enrollment Phase |
|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1219 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 43 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 307 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 27 Participants |
| Race (NIH/OMB) White | 935 Participants |
| Sex: Female, Male Female | 427 Participants |
| Sex: Female, Male Male | 853 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 19 / 1,269 | 155 / 495 | 154 / 495 |
| other Total, other adverse events | 1,153 / 1,269 | 227 / 495 | 358 / 495 |
| serious Total, serious adverse events | 259 / 1,269 | 42 / 495 | 88 / 495 |
Outcome results
Primary
DFS in All Randomized Stage II-IIIA Population
DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in participants with disease stage II-IIIA. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
Time frame: Up to 95 months
Population: Stage II-IIIA population was defined as all randomized participants with extent of disease as either Stage II or Stage IIIA, and is a subset of the ITT population. Randomized ITT population was defined as all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | DFS in All Randomized Stage II-IIIA Population | 57.4 months |
| Best Supportive Care (BSC) | DFS in All Randomized Stage II-IIIA Population | 40.8 months |
95% CI: [0.691, 0.998]
Primary
DFS in the Programmed Death-ligand 1 (PD-L1) SP263 ≥ 1% Tumor Cell (TC) Subpopulation Within the Stage II-IIIA Population
DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in PD-L1 ≥1% subpopulation within the Stage II-IIIA population. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
Time frame: Up to 95 months
Population: PD-L1 subpopulation, defined as ≥1% TC expression by the SP263 immunohistochemistry (IHC) assay, included Stage II-IIIA population with valid PD-L1 SP263 measurement at baseline. Stage II-IIIA population included all randomized participants with extent of disease as either Stage II or Stage III, \& is a subset of ITT population. Randomized ITT population included all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | DFS in the Programmed Death-ligand 1 (PD-L1) SP263 ≥ 1% Tumor Cell (TC) Subpopulation Within the Stage II-IIIA Population | 68.5 months |
| Best Supportive Care (BSC) | DFS in the Programmed Death-ligand 1 (PD-L1) SP263 ≥ 1% Tumor Cell (TC) Subpopulation Within the Stage II-IIIA Population | 37.3 months |
95% CI: [0.545, 0.91]
Primary
Disease-Free Survival (DFS) in Intent-to-treat (ITT) Population
DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
Time frame: Up to 95 months
Population: Randomized ITT population was defined as all randomized participants with resected Stage IB \[tumors ≥ 4 centimetres (cm)\]-IIIA NSCLC whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | Disease-Free Survival (DFS) in Intent-to-treat (ITT) Population | 65.6 months |
| Best Supportive Care (BSC) | Disease-Free Survival (DFS) in Intent-to-treat (ITT) Population | 47.8 months |
p-value: 0.068395% CI: [0.71, 1.013]Log Rank
Secondary
DFS in the PD-L1 (SP263 ≥ 50% TC) Subpopulation Within the Stage II-IIIA Population
DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
Time frame: Up to 95 months
Population: PD-L1 subpopulation, defined as ≥50% TC expression by the SP263 IHC assay, included Stage II-IIIA population with valid PD-L1 SP263 measurement at baseline. Stage II-IIIA population included all randomized participants with extent of disease as either Stage II or Stage III, \& is a subset of ITT population. Randomized ITT population included all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab | DFS in the PD-L1 (SP263 ≥ 50% TC) Subpopulation Within the Stage II-IIIA Population | NA months |
| Best Supportive Care (BSC) | DFS in the PD-L1 (SP263 ≥ 50% TC) Subpopulation Within the Stage II-IIIA Population | 41.1 months |
95% CI: [0.332, 0.761]
Secondary
Disease-free Rate at Year 3 in All Randomized Stage II-IIIA Population
DFS rate was defined as percentage of participants who were disease-free at Year 3. DFS rate was analyzed in participants with disease stage II-IIIA. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Time frame: Year 3
Population: Stage II-IIIA population was defined as all randomized participants with extent of disease as either Stage II or Stage III, and is a subset of the ITT population. Randomized ITT population was defined as all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether or not the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Disease-free Rate at Year 3 in All Randomized Stage II-IIIA Population | 59.30 percentage of participants |
| Best Supportive Care (BSC) | Disease-free Rate at Year 3 in All Randomized Stage II-IIIA Population | 52.64 percentage of participants |
95% CI: [-0.06, 13.36]
Secondary
Disease-free Rate at Year 3 in ITT Population
DFS rate was defined as percentage of participants who were disease-free at Year 3. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Time frame: Year 3
Population: Randomized ITT population was defined as all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether or not the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Disease-free Rate at Year 3 in ITT Population | 61.43 percentage of participants |
| Best Supportive Care (BSC) | Disease-free Rate at Year 3 in ITT Population | 55.45 percentage of participants |
95% CI: [-0.28, 12.23]
Secondary
Disease-free Rate at Year 3 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population
DFS rate was defined as percentage of participants who were disease-free at Year 3. DFS rate was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Time frame: Year 3
Population: PD-L1 subpopulation, defined as ≥ 1% TC expression by the SP263 IHC assay, included Stage II-IIIA population with valid PD-L1 SP263 measurement at baseline. Stage II-IIIA population included all randomized participants with extent of disease as either Stage II or Stage III, \& is a subset of ITT population. Randomized ITT population included all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Disease-free Rate at Year 3 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population | 62.72 percentage of participants |
| Best Supportive Care (BSC) | Disease-free Rate at Year 3 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population | 52.05 percentage of participants |
95% CI: [1.56, 19.79]
Secondary
Disease-free Rate at Year 5 in All Randomized Stage II-IIIA Population
DFS rate was defined as percentage of participants who were disease-free at Year 5. DFS rate was analyzed in participants with disease stage II-IIIA. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Time frame: Year 5
Population: Stage II-IIIA population was defined as all randomized participants with extent of disease as either Stage II or Stage III, and is a subset of the ITT population. Randomized ITT population was defined as all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether or not the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Disease-free Rate at Year 5 in All Randomized Stage II-IIIA Population | 49.28 percentage of participants |
| Best Supportive Care (BSC) | Disease-free Rate at Year 5 in All Randomized Stage II-IIIA Population | 44.40 percentage of participants |
95% CI: [-1.94, 11.7]
Secondary
Disease-free Rate at Year 5 in ITT Population
DFS rate was defined as percentage of participants who were disease-free at Year 5. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Time frame: Year 5
Population: Randomized ITT population was defined as all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether or not the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Disease-free Rate at Year 5 in ITT Population | 51.96 percentage of participants |
| Best Supportive Care (BSC) | Disease-free Rate at Year 5 in ITT Population | 46.48 percentage of participants |
95% CI: [-0.94, 11.9]
Secondary
Disease-free Rate at Year 5 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population
DFS rate was defined as percentage of participants who were disease-free at Year 5. DFS rate was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Time frame: Year 5
Population: PD-L1 subpopulation, defined as ≥ 1% TC expression by the SP263 IHC assay, included Stage II-IIIA population with valid PD-L1 SP263 measurement at baseline. Stage II-IIIA population included all randomized participants with extent of disease as either Stage II or Stage III, \& is a subset of ITT population. Randomized ITT population included all randomized participants with resected Stage IB (tumors ≥ 4 cm)-IIIA NSCLC whether the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Disease-free Rate at Year 5 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population | 53.15 percentage of participants |
| Best Supportive Care (BSC) | Disease-free Rate at Year 5 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population | 42.69 percentage of participants |
95% CI: [1.16, 19.76]
Secondary
Maximum Plasma Concentration (Cmax) of Atezolizumab
Time frame: 30 min post-infusion on Day 1 of Cycle 1 (Cycle length = 21 days)
Population: PK-evaluable population was defined as all randomized participants who received any dose of the study treatment and who have evaluable pharmacokinetic samples. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atezolizumab | Maximum Plasma Concentration (Cmax) of Atezolizumab | 367 micrograms/millilitres (μg/ml) | Geometric Coefficient of Variation 124 |
Secondary
Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab
Time frame: Prior to infusion on Day 1 of Cycles 1, 2, 3, 4, 8, 16 (Cycle length = 21 days), at study discontinuation visit (up to 12 months), Day 120 post last dose of atezolizumab (up to 16 months)
Population: PK-evaluable population was defined as all randomized participants who received any dose of the study treatment and who have evaluable pharmacokinetic samples. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Cycle 1 Day 1 | 367 μg/ml | Geometric Coefficient of Variation 123.5 |
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Cycle 2 Day 1 | 87.8 μg/ml | Geometric Coefficient of Variation 79.3 |
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Cycle 3 Day 1 | 141 μg/ml | Geometric Coefficient of Variation 58.4 |
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Cycle 4 Day 1 | 170 μg/ml | Geometric Coefficient of Variation 57.6 |
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Cycle 8 Day 1 | 222 μg/ml | Geometric Coefficient of Variation 40.6 |
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Cycle 16 Day 1 | 221 μg/ml | Geometric Coefficient of Variation 87.3 |
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Treatment Discontinuation Visit | 148 μg/ml | Geometric Coefficient of Variation 221.8 |
| Atezolizumab | Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab | Day 120 Post Last Dose of Atezolizumab | 8.58 μg/ml | Geometric Coefficient of Variation 794.8 |
Secondary
Overall Survival (OS) in the ITT Population
OS was defined as the time from randomization to death from any cause.
Time frame: Up to 20 years
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant when administered a pharmaceutical product regardless of the causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product.
Time frame: Up to 20 years
Secondary
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
The percentage of ATA (Also called anti-drug antibodies (ADA))-positive participants after drug administration were determined for participants exposed to atezolizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result.
Time frame: Predose (Hour 0) on Day 1 of Cycles 2, 3, 4, 8, 16 (Cycle length = 21 days), at treatment discontinuation (TD) (up to 12 months), 120 days after last atezolizumab administration (up to 16 months)
Population: ADA evaluable population was defined as all randomized participants who received at least one dose of atezolizumab and who have at least one post-baseline ADA result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | 31.2 percentage of participants |