| Secondary | PFS in the FAS | PFS was defined as the time from randomization to the first documented PD as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. | FAS: All randomized participants, whether or not the participant received the assigned treatment. | Posted | | Median | 95% Confidence Interval | months | | From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
| | | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0005.42(4.47 to 5.65)
- OG0015.06(4.40 to 5.42)
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| Stratification factors were LDH (> ULN vs. ≤ ULN) and ECOG (0 vs. 1). | Log Rank | | 0.4440 | | Hazard Ratio (HR) | 1.08 | | | 2-Sided | 95 | 0.89 | 1.31 | | | | | Superiority | | |
|
| Secondary | OS in the FAS | OS was defined as the time from randomization to death from any cause. | FAS: All randomized participants, whether or not the participant received the assigned treatment. | Posted | | Median | 95% Confidence Interval | months | | From randomization to death from any cause (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Investigator-assessed Confirmed Objective Response Rate (ORR) in the PAS | ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off. | PAS: All randomized participants without presence or history of brain metastases at baseline. | Posted | | Number | 95% Confidence Interval | percentage of participants | | From randomization up to approximately 24 months | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Investigator-assessed Confirmed ORR in the FAS | ORR was defined as the percentage of participants with CR or PR as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off. | FAS: All randomized participants, whether or not the participant received the assigned treatment. | Posted | | Number | 95% Confidence Interval | percentage of participants | | From randomization up to approximately 24 months | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Investigator-assessed Duration of Response (DOR) in the PAS | DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD or death from any cause, whichever occurred first, as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. | PAS: All randomized participants without presence or history of brain metastases at baseline. DOR was analyzed in confirmed responders by investigator. | Posted | | Median | 95% Confidence Interval | months | | From the first occurrence of a documented confirmed objective response (OR) to PD or death from any cause, whichever occurred first (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Investigator-assessed DOR in the FAS | DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD or death from any cause, whichever occurred first, as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. | FAS: All randomized participants, whether or not the participant received the assigned treatment. DOR was analyzed in confirmed responders by investigator. | Posted | | Median | 95% Confidence Interval | months | | From the first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Investigator-assessed PFS Rates at 6 Months and 12 Months in the PAS | PFS rate at 6 months and 12 months was defined as the percentage of participants who were event-free at these specific time points. Percentages have been rounded off to the nearest decimal point. A point estimate of the event-free rate was a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value was calculated from ordered data (Event, Censoring) of each participant, using the Kaplan-Meier (K-M) method, accounting for censored observations (so event-free rates may not directly be calculated based only on participants remaining at risk). | PAS: All randomized participants without presence or history of brain metastases at baseline. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Month 6, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Investigator-assessed PFS Rates at 6 Months and 12 Months in the FAS | PFS rate at 6 months and 12 months was defined as the percentage of participants who were event-free at these specific time points. Percentages have been rounded off to the nearest decimal point. A point estimate of the event-free rate was a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value was calculated from ordered data (Event, Censoring) of each participant, using the K-M method, accounting for censored observations (so event-free rates may not directly be calculated based only on participants remaining at risk). | FAS: All randomized participants, whether or not the participant received the assigned treatment. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Month 6, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | OS Rates at 12 Months and 24 Months in the PAS | OS rate at 12 months and 24 months was defined as the percentage of participants who were alive at these specific time points. Percentages have been rounded off to the nearest decimal point. A point estimate of the event-free rate was a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value was calculated from ordered data (Event, Censoring) of each participant, using the K-M method, accounting for censored observations (so event-free rates may not directly be calculated based only on participants remaining at risk). | PAS: All randomized participants without presence or history of brain metastases at baseline. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Month 12, Month 24 | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | |
|
| Secondary | OS Rates at 12 Months and 24 Months in the FAS | OS rate at 12 months and 24 months was defined as the percentage of participants who were alive at these specific time points. Percentages have been rounded off to the nearest decimal point. A point estimate of the event-free rate was a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value was calculated from ordered data (Event, Censoring) of each participant, using the K-M method, accounting for censored observations (so event-free rates may not directly be calculated based only on participants remaining at risk). | FAS: All randomized participants, whether or not the participant received the assigned treatment. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Month 12, Month 24 | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | |
|
| Secondary | Time to Confirmed Deterioration (TTCD) of European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (PF) in the PAS | TTCD was the time from randomization until the first confirmed clinically meaningful deterioration in PF. TTCD was determined based on patient-reported PF (Items 1-5) as collected and measured by the EORTC QLQ-C30. The PF was measured on 4-point scale (1='Not at all' to 4='Very much'). A high score for the PF subscale represented a high/healthy level of functioning. The scale was linearly transformed so that each score ranged from 0 to 100. A score change of at least 10-point in PF subscale score was perceived by participants as clinically meaningful. Confirmed clinically meaningful deterioration was defined as a clinically meaningful decrease from baseline that was held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 3 weeks. | PAS: All randomized participants without presence or history of brain metastases at baseline. | Posted | | Median | 95% Confidence Interval | months | | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | TTCD of EORTC QLQ-C30 Physical Functioning in the FAS | TTCD was the time from randomization until the first confirmed clinically meaningful deterioration in PF. TTCD was determined based on patient-reported PF (Items 1-5) as collected and measured by the EORTC QLQ-C30. The PF was measured on 4-point scale (1='Not at all' to 4='Very much'). A high score for the PF subscale represented a high/healthy level of functioning. The scale was linearly transformed so that each score ranged from 0 to 100. A score change of at least 10-point in PF subscale score was perceived by participants as clinically meaningful. Confirmed clinically meaningful deterioration was defined as a clinically meaningful decrease from baseline that was held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 3 weeks. | FAS: All randomized participants, whether or not the participant received the assigned treatment. | Posted | | Median | 95% Confidence Interval | months | | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | TTCD of EORTC QLQ-C30 Global Health Status (GHS)/Quality-of-life (QoL) in the PAS | TTCD was the time from randomization until the first confirmed clinically meaningful deterioration in patient-reported GHS/QoL. TTCD was determined based on patient-reported GHS/QoL (Items 29-30) as collected and measured by the EORTC QLQ-C30. GHS/QoL items were scored on a 7-point scale, ranging from "very poor" to "excellent". A high score for the GHS/QoL subscale represented a high health-related QoL. The scale was linearly transformed so that each score ranged from 0 to 100. A score change of at least 10-point in GHS/QoL subscale score was perceived by participants as clinically meaningful. Confirmed clinically meaningful deterioration was defined as a clinically meaningful decrease from baseline that was held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 3 weeks. | PAS: All randomized participants without presence or history of brain metastases at baseline. | Posted | | Median | 95% Confidence Interval | months | | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | TTCD of EORTC QLQ-C30 GHS/QoL in the FAS | TTCD was the time from randomization until the first confirmed clinically meaningful deterioration in patient-reported GHS/QoL. TTCD was determined based on patient-reported GHS/QoL (Items 29-30) as collected and measured by the EORTC QLQ-C30. GHS/QoL items were scored on a 7-point scale, ranging from "very poor" to "excellent". A high score for the GHS/QoL subscale represented a high health-related QoL. The scale was linearly transformed so that each score ranged from 0 to 100. A score change of at least 10-point in GHS/QoL subscale score was perceived by participants as clinically meaningful. Confirmed clinically meaningful deterioration was defined as a clinically meaningful decrease from baseline that was held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 3 weeks. | FAS: All randomized participants, whether or not the participant received the assigned treatment. | Posted | | Median | 95% Confidence Interval | months | | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study were also considered as AEs. | Safety-evaluable set: All randomized participants who received at least one dose of study treatment. | Posted | | Count of Participants | | Participants | | Up to 58 months | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Number of Participants With Severity of Cytokine-release Syndrome (CRS), as Determined by the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Scale | CRS=supraphysiologic response following administration of any immune therapy that results in activation/engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms may be progressive, including fever at onset, and may also include hypotension, capillary leak (hypoxia), and end-organ dysfunction. Severity of CRS was determined per ASTCT Consensus Grading Criteria, which categorizes CRS into 5 grades: Grade 1: Fever (≥38◦Celsius), with/without constitutional symptoms, in absence of hypotension & hypoxia; Grade 2: Fever with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen; Grade 3: Fever with hypotension requiring one vasopressor, with/without vasopressin, and/or hypoxia requiring high-flow oxygen; Grade 4: Fever accompanied by hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive-pressure ventilation; Grade 5: death due to CRS. Only non zero values have been reported. | Safety-evaluable set: All randomized participants who received at least one dose of study treatment. | Posted | | Count of Participants | | Participants | | Up to 58 months | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Minimum Serum Concentration (Cmin) of Tiragolumab | | Pharmacokinetic (PK)-evaluable set: All participants who received at least one dose of tiragolumab and who had at least one post-baseline PK sample available. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Geometric Mean | Geometric Coefficient of Variation | micrograms/milliliter (µg/mL) | | At the end of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days) | | | | ID | Title | Description |
|---|
| OG000 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
| |
| Secondary | Cmin of Atezolizumab | | PK-evaluable set: All participants who received at least one dose of atezolizumab and who had at least one post-baseline PK sample available. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Geometric Mean | Geometric Coefficient of Variation | µg/mL | | At the end of each Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
|
| Secondary | Maximum Serum Concentration (Cmax) of Tiragolumab | | PK-evaluable set: All participants who received at least one dose of tiragolumab and who had at least one post-baseline PK sample available. Overall number of participants analyzed is the number of participants with data available for analysis. | Posted | | Geometric Mean | Geometric Coefficient of Variation | µg/mL | | Pre-dose and 30 minutes post end of infusion (EOI) on Day 1 of Cycle 1 (1 Cycle=21 days) | | | | ID | Title | Description |
|---|
| OG000 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
| |
| Secondary | Cmax of Atezolizumab | | PK-evaluable set: All participants who received at least one dose of atezolizumab and who had at least one post-baseline PK sample available. Overall number analyzed is the number of participants with data available for analysis. | Posted | | Geometric Mean | Geometric Coefficient of Variation | µg/mL | | Pre-dose and 30 minutes post EOI on Day 1 of Cycle 1 (1 Cycle=21 days) | | | | ID | Title | Description |
|---|
| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
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| Secondary | Number of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab | Participants were considered to be ADA-positive if they were ADA-negative at baseline but developed an ADA response following tiragolumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such at least 0.60 titer unit (t.u.) greater than the baseline titer result (treatment-enhanced ADA response). The total number of participants who developed ADAs to tiragolumab was determined by summing the ADA-positive participants across all timepoints. | Tiragolumab ADA-evaluable set: All participants who received at least one dose of tiragolumab treatment and with an ADA assay result from at least one sample result. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Count of Participants | | Participants | | Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8,12, 16 and at treatment discontinuation (TD) visit (up to 24 months) (1 Cycle=21 days) | | | | ID | Title | Description |
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| OG000 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
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| Secondary | Number of Participants With ADAs to Atezolizumab | Participants were considered to be ADA-positive if they were ADA-negative at baseline but developed an ADA response following atezolizumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such at least 0.60 t.u. greater than the baseline titer result (treatment-enhanced ADA response). The total number of participants who developed ADAs to tiragolumab was determined by summing the ADA-positive participants across all timepoints. | Atezolizumab ADA-evaluable set: All participants who received at least one dose of atezolizumab treatment and with an ADA assay result from at least one sample result. Number analyzed is the number of participants with data available for analysis at the specified timepoints. | Posted | | Count of Participants | | Participants | | Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8,12, 16 and at TD visit (up to 24 months) (1 Cycle=21 days) | | | | ID | Title | Description |
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| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
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| Other Pre-specified | Change From Baseline in EuroQol 5-dimension, 5-level (EQ-5D-5L) Index-based and Visual Analog Scale Scores | The EQ-5D-5L is a validated self-report health status questionnaire that was used to calculate a health status utility score for use in health economic analyses. There were two components to the EQ-5D-5L: a five-item health state profile that assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analog scale (VAS) that measured health state. The EQ VAS records the participant's self-rated health on a vertical visual analogue scale ranging from 0 to 100. A single composite score was calculated based on the responses as an indicator of the participant's health status. The scale ranges 0-100, 0=worst health and 100=best health. | | Not Posted | | | | | | Pre-dose; Day 1 of Cycles 1, 2, 3, and 4 | | Participants | | | | |
| Primary | Investigator-assessed Progression-free Survival (PFS) in the Primary Analysis Set (PAS) | PFS was defined as the time from randomization to the first documented PD as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm). | PAS: All randomized participants without presence or history of brain metastases at baseline. | Posted | | Median | 95% Confidence Interval | months | | From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months) | | | | ID | Title | Description |
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| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab |
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| Primary | Overall Survival (OS) in the PAS | OS was defined as the time from randomization to death from any cause. | PAS: All randomized participants without presence or history of brain metastases at baseline. | Posted | | Median | 95% Confidence Interval | months | | From randomization to death from any cause (up to approximately 24 months) | | | | ID | Title | Description |
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| OG000 | Arm A: Placebo + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. | | OG001 | Arm B: Tiragolumab + Atezolizumab | During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit. |
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