Small Cell Lung Cancer
Conditions
Brief summary
This study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), LDH (\</= upper limit of normal \[ULN\] vs. \> ULN), and presence or history of brain metastasis (yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment regimens during induction phase: * Arm A: Tiragolumab plus atezolizumab plus CE * Arm B: Placebo plus atezolizumab plus CE Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).
Interventions
DRUGTiragolumab
Tiragolumab 600 milligrams (mg) administered by IV infusion on Day 1 of each 21-day cycle.
DRUGAtezolizumab
Atezolizumab 1200 mg administered by IV infusion on Day 1 of each 21-day cycle.
DRUGCarboplatin
Carboplatin was administered by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
DRUGEtoposide
Etoposide 100 mg/m\^2 administered by IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles.
DRUGPlacebo
Placebo administered by IV infusion on Day 1 of each 21-day cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC) * No prior systemic treatment for ES-SCLC * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) * Adequate hematologic and end-organ function * Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC
Exclusion criteria
* Symptomatic or actively progressing central nervous system (CNS) metastases * Malignancies other than small cell lung cancer (SCLC) within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * Positive test result for human immunodeficiency virus (HIV) * Active hepatitis B or hepatitis C * Severe infection at the time of randomization * Treatment with any other investigational agent within 28 days prior to initiation of study treatment * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4), anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies * Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Progression-free Survival (PFS) in the Primary Analysis Set (PAS) | From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months) | 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). |
| Overall Survival (OS) in the PAS | From randomization to death from any cause (up to approximately 24 months) | OS was defined as the time from randomization to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS in the FAS | From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months) | 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. |
| OS in the FAS | From randomization to death from any cause (up to approximately 24 months) | OS was defined as the time from randomization to death from any cause. |
| Investigator-assessed Confirmed Objective Response Rate (ORR) in the PAS | From randomization up to approximately 24 months | 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. |
| Investigator-assessed Confirmed ORR in the FAS | From randomization up to approximately 24 months | 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. |
| Investigator-assessed Duration of Response (DOR) in the PAS | 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) | 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. |
| Investigator-assessed DOR in the FAS | From the first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 24 months) | 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. |
| Investigator-assessed PFS Rates at 6 Months and 12 Months in the PAS | Month 6, Month 12 | 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). |
| Investigator-assessed PFS Rates at 6 Months and 12 Months in the FAS | Month 6, Month 12 | 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). |
| OS Rates at 12 Months and 24 Months in the PAS | Month 12, Month 24 | 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). |
| OS Rates at 12 Months and 24 Months in the FAS | Month 12, Month 24 | 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). |
| 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 | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | 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. |
| TTCD of EORTC QLQ-C30 Physical Functioning in the FAS | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | 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. |
| TTCD of EORTC QLQ-C30 Global Health Status (GHS)/Quality-of-life (QoL) in the PAS | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | 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. |
| TTCD of EORTC QLQ-C30 GHS/QoL in the FAS | From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months) | 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. |
| Number of Participants With Adverse Events (AEs) | Up to 58 months | 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. |
| 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 | Up to 58 months | 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. |
| Minimum Serum Concentration (Cmin) of Tiragolumab | At the end of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days) | — |
| Cmin of Atezolizumab | At the end of each Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days) | — |
| Maximum Serum Concentration (Cmax) of Tiragolumab | Pre-dose and 30 minutes post end of infusion (EOI) on Day 1 of Cycle 1 (1 Cycle=21 days) | — |
| Cmax of Atezolizumab | Pre-dose and 30 minutes post EOI on Day 1 of Cycle 1 (1 Cycle=21 days) | — |
| Number of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab | 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) | 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. |
| Number of Participants With ADAs to Atezolizumab | 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) | 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. |
Countries
Australia, Austria, Belgium, Brazil, Czechia, Germany, Greece, Hungary, Italy, Japan, Netherlands, New Zealand, Poland, Russia, Serbia, Singapore, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 490 participants with untreated extensive-stage small cell lung cancer (ES-SCLC) took part in the study at 121 centers across 23 countries from 04 February 2020 to 31 July 2025.
Pre-assignment details
Participants were randomized to receive Placebo + Atezolizumab (P+A) or Tiragolumab + Atezolizumab (T+A) with carboplatin & etoposide as induction treatment, followed by either P+A or T+A as maintenance treatment. 1 participant from P+A arm and 4 from T+A arm were randomized but not treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Atezolizumab During induction treatment participants received atezolizumab, 1200 milligram (mg) followed by placebo and carboplatin, as intravenous (IV) infusion, to achieve an initial target area under the concentration-time curve (AUC) of 5 milligram/milliliter/minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 cycles. Etoposide 100 milligram per square meter (mg/m\^2) was also administered as IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles. Participants then received maintenance treatment with atezolizumab+ placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until disease progression or loss of clinical benefit. | 247 |
| Tiragolumab + Atezolizumab During induction treatment participants received atezolizumab, 1200 mg followed by tiragolumab, 600mg and carboplatin, as IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Etoposide 100 mg/m\^2 was also administered as IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles. Participants then received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until disease progression or loss of clinical benefit. | 243 |
| Total | 490 |
Baseline characteristics
| Characteristic | Placebo + Atezolizumab | Tiragolumab + Atezolizumab | Total |
|---|---|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 7.9 | 64.5 years STANDARD_DEVIATION 8.2 | 64.8 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 10 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 229 Participants | 224 Participants | 453 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 9 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 67 Participants | 63 Participants | 130 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) White | 174 Participants | 173 Participants | 347 Participants |
| Sex: Female, Male Female | 83 Participants | 81 Participants | 164 Participants |
| Sex: Female, Male Male | 164 Participants | 162 Participants | 326 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 200 / 247 | 207 / 243 |
| other Total, other adverse events | 235 / 246 | 228 / 239 |
| serious Total, serious adverse events | 108 / 246 | 109 / 239 |
Outcome results
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 disease progression (PD) as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. PD: 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).
Time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
Population: Primary analysis set (PAS): All randomized participants without presence or history of brain metastases at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS) | 5.55 months |
| Tiragolumab + Atezolizumab | Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS) | 5.36 months |
Comparison: Stratification factors were LDH (\> upper limit of normal \[ULN\] vs. \</= ULN) and Eastern Cooperative Oncology Group (ECOG; 0 vs. 1).p-value: 0.350495% CI: [0.89, 1.38]Log Rank
Primary
Overall Survival (OS) in the PAS
OS was defined as the time from randomization to death from any cause.
Time frame: From randomization to death from any cause (up to approximately 24 months)
Population: PAS: All randomized participants without presence or history of brain metastases at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | Overall Survival (OS) in the PAS | 13.14 months |
| Tiragolumab + Atezolizumab | Overall Survival (OS) in the PAS | 13.11 months |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.285995% CI: [0.9, 1.44]Log Rank
Secondary
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.
Time frame: From baseline up to 65 months
Secondary
Cmax of Atezolizumab
Time frame: Predose and 30 minutes post EOI on Day 1 of Cycle 1 (each cycle is 21 days)
Population: PK-evaluable set: All participants who received at least one dose of study treatment and who had at least one post-baseline PK sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Atezolizumab | Cmax of Atezolizumab | 398 mcg/mL | Geometric Coefficient of Variation 28.2 |
| Tiragolumab + Atezolizumab | Cmax of Atezolizumab | 405 mcg/mL | Geometric Coefficient of Variation 23 |
Secondary
Cmin of Atezolizumab
Time frame: At the end of each cycle (each cycle is 21 days) of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months)
Population: PK-evaluable set: All participants who received at least one dose of study treatment 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 analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Atezolizumab | Cmin of Atezolizumab | Cycle 15 | 198 mcg/mL | Geometric Coefficient of Variation 75.5 |
| Placebo + Atezolizumab | Cmin of Atezolizumab | Cycle 1 | 75.0 mcg/mL | Geometric Coefficient of Variation 63.2 |
| Placebo + Atezolizumab | Cmin of Atezolizumab | Cycle 2 | 121 mcg/mL | Geometric Coefficient of Variation 55.8 |
| Placebo + Atezolizumab | Cmin of Atezolizumab | Cycle 3 | 144 mcg/mL | Geometric Coefficient of Variation 49.8 |
| Placebo + Atezolizumab | Cmin of Atezolizumab | Cycle 7 | 205 mcg/mL | Geometric Coefficient of Variation 45.3 |
| Placebo + Atezolizumab | Cmin of Atezolizumab | Cycle 11 | 226 mcg/mL | Geometric Coefficient of Variation 37.3 |
| Tiragolumab + Atezolizumab | Cmin of Atezolizumab | Cycle 7 | 198 mcg/mL | Geometric Coefficient of Variation 46.4 |
| Tiragolumab + Atezolizumab | Cmin of Atezolizumab | Cycle 15 | 253 mcg/mL | Geometric Coefficient of Variation 36.6 |
| Tiragolumab + Atezolizumab | Cmin of Atezolizumab | Cycle 3 | 155 mcg/mL | Geometric Coefficient of Variation 81.5 |
| Tiragolumab + Atezolizumab | Cmin of Atezolizumab | Cycle 1 | 75.4 mcg/mL | Geometric Coefficient of Variation 70.8 |
| Tiragolumab + Atezolizumab | Cmin of Atezolizumab | Cycle 11 | 244 mcg/mL | Geometric Coefficient of Variation 37 |
| Tiragolumab + Atezolizumab | Cmin of Atezolizumab | Cycle 2 | 125 mcg/mL | Geometric Coefficient of Variation 38.4 |
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 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.
Time frame: From randomization up to approximately 24 months
Population: PAS: All randomized participants without presence or history of brain metastases at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Atezolizumab | Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS | 66.7 percentage of participants |
| Tiragolumab + Atezolizumab | Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS | 73.5 percentage of participants |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.141895% CI: [-2.57, 15.99]Cochran-Mantel-Haenszel
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 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.
Time frame: From randomization up to approximately 24 months
Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Atezolizumab | Investigator-Assessed Confirmed ORR in the FAS | 65.6 percentage of participants |
| Tiragolumab + Atezolizumab | Investigator-Assessed Confirmed ORR in the FAS | 70.8 percentage of participants |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.219195% CI: [-3.33, 13.61]Cochran-Mantel-Haenszel
Secondary
Investigator-Assessed DOR in the FAS
DOR was defined as the time from the first occurrence of a documented OR 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 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= 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.
Time frame: From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
Population: FAS: All randomized participants, whether or not the participant received the assigned treatment. DOR was analyzed in confirmed responders by investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | Investigator-Assessed DOR in the FAS | 5.11 months |
| Tiragolumab + Atezolizumab | Investigator-Assessed DOR in the FAS | 4.17 months |
Secondary
Investigator-Assessed Duration of Response (DOR) in the PAS
DOR was defined as the time from the first occurrence of a documented objective response (OR) 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 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= 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.
Time frame: From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
Population: PAS: All randomized participants without presence or history of brain metastases at baseline. DOR was analyzed in confirmed responders by investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | Investigator-Assessed Duration of Response (DOR) in the PAS | 5.59 months |
| Tiragolumab + Atezolizumab | Investigator-Assessed Duration of Response (DOR) in the PAS | 4.19 months |
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 is a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value is calculated from ordered data (Event, Censoring) of each patient, using the Kaplan-Meier method, and accounts for censored observations( so Event free rates may not directly be calculated based only on patients remaining at risk).
Time frame: Month 6, Month 12
Population: 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 analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS | Month 6 | 37.95 percentage of participants |
| Placebo + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS | Month 12 | 14.07 percentage of participants |
| Tiragolumab + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS | Month 6 | 31.30 percentage of participants |
| Tiragolumab + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS | Month 12 | 12.33 percentage of participants |
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 is a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value is calculated from ordered data (Event, Censoring) of each patient, using the Kaplan-Meier method, and accounts for censored observations( so Event free rates may not directly be calculated based only on patients remaining at risk).
Time frame: Month 6, Month 12
Population: 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 analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS | Month 6 | 42.42 percentage of participants |
| Placebo + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS | Month 12 | 17.29 percentage of participants |
| Tiragolumab + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS | Month 6 | 35.15 percentage of participants |
| Tiragolumab + Atezolizumab | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS | Month 12 | 14.21 percentage of participants |
Secondary
Maximum Serum Concentration (Cmax) of Tiragolumab
Time frame: Predose and 30 minutes post end of infusion (EOI) on Day 1 of Cycle 1 (each cycle is 21 days)
Population: PK-evaluable set: All participants who received at least one dose of study treatment 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 analyses
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Atezolizumab | Maximum Serum Concentration (Cmax) of Tiragolumab | 188 mcg/mL | Geometric Coefficient of Variation 24.2 |
Secondary
Minimum Serum Concentration (Cmin) of Tiragolumab
Time frame: At the end of each cycle (each cycle is 21 days) of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months)
Population: PK-evaluable set: All participants who received at least one dose of study treatment and who had at least one post-baseline PK sample available. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Atezolizumab | Minimum Serum Concentration (Cmin) of Tiragolumab | Cycle 1 | 29.5 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 49.2 |
| Placebo + Atezolizumab | Minimum Serum Concentration (Cmin) of Tiragolumab | Cycle 2 | 46.5 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 47.5 |
| Placebo + Atezolizumab | Minimum Serum Concentration (Cmin) of Tiragolumab | Cycle 3 | 56.3 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 83.5 |
| Placebo + Atezolizumab | Minimum Serum Concentration (Cmin) of Tiragolumab | Cycle 7 | 76.3 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 48.2 |
| Placebo + Atezolizumab | Minimum Serum Concentration (Cmin) of Tiragolumab | Cycle 11 | 78.8 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 246 |
| Placebo + Atezolizumab | Minimum Serum Concentration (Cmin) of Tiragolumab | Cycle 15 | 96.4 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 43.8 |
Secondary
Number of Participants With ADAs to Atezolizumab
Reported here is the number of participants who had a positive ADA assay result at baseline and the number of participants positive for treatment emergent ADAs. The number of participants positive for treatment emergent ADAs includes treatment-induced and treatment-enhanced ADA positive participants. Treatment-induced ADAs are participants with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADAs are participants with a positive ADA result at baseline who had one or more post-baseline titer results that were at least 0.60 t.u. greater than the baseline titer result. The total number of participants who developed ADAs to atezolizumab was determined by summing the ADA-positive participants across all timepoints.
Time frame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 24 months)
Population: 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 analyses at the specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Participants with Positive Sample at Baseline | 2 Participants |
| Placebo + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Participants positive for Treatment Emergent ADAs | 48 Participants |
| Placebo + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Treatment-induced ADAs | 48 Participants |
| Placebo + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Treatment-enhanced ADAs | 0 Participants |
| Tiragolumab + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Treatment-enhanced ADAs | 0 Participants |
| Tiragolumab + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Participants with Positive Sample at Baseline | 1 Participants |
| Tiragolumab + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Treatment-induced ADAs | 22 Participants |
| Tiragolumab + Atezolizumab | Number of Participants With ADAs to Atezolizumab | Participants positive for Treatment Emergent ADAs | 22 Participants |
Secondary
Number of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Reported here is the number of participants who had a positive ADA assay result at baseline and the number of participants positive for treatment emergent ADAs. The participants positive for treatment emergent ADAs include treatment-induced and treatment-enhanced ADA positive participants. Treatment-induced ADAs are participants with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADAs are participants with a positive ADA result at baseline who had one or more post-baseline titer results that were at least 0.60 t.u. greater than the baseline titer result. The total number of participants who developed ADAs to tiragolumab was determined by summing the ADA-positive participants across all timepoints.
Time frame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 24 months)
Population: 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. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + Atezolizumab | Number of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab | Participants with Positive Sample at Baseline | 2 Participants |
| Placebo + Atezolizumab | Number of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab | Participants positive for Treatment Emergent ADAs | 3 Participants |
| Placebo + Atezolizumab | Number of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab | Treatment-induced ADAs | 3 Participants |
| Placebo + Atezolizumab | Number of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab | Treatment-enhanced ADAs | 0 Participants |
Secondary
OS in the FAS
OS was defined as the time from randomization to death from any cause.
Time frame: From randomization to death from any cause (up to approximately 24 months)
Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | OS in the FAS | 12.91 months |
| Tiragolumab + Atezolizumab | OS in the FAS | 12.75 months |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.420595% CI: [0.88, 1.35]Log Rank
Secondary
Overall Survival Rates at 12 Months and 24 Months in the FAS
Overall survival 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 is a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value is calculated from ordered data (Event, Censoring) of each patient, using the Kaplan-Meier method, and accounts for censored observations( so Event free rates may not directly be calculated based only on patients remaining at risk).
Time frame: Month 12, Month 24
Population: 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 analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the FAS | Month 12 | 55.84 percentage of participants |
| Placebo + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the FAS | Month 24 | 25.82 percentage of participants |
| Tiragolumab + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the FAS | Month 12 | 52.82 percentage of participants |
| Tiragolumab + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the FAS | Month 24 | 20.53 percentage of participants |
Comparison: Month 12p-value: 0.505995% CI: [-11.92, 5.88]Z-test
Comparison: Month 24p-value: 0.245895% CI: [-14.23, 3.65]Z-test
Secondary
Overall Survival Rates at 12 Months and 24 Months in the PAS
Overall survival 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 is a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value is calculated from ordered data (Event, Censoring) of each patient, using the Kaplan-Meier method, and accounts for censored observations( so Event free rates may not directly be calculated based only on patients remaining at risk).
Time frame: Month 12, Month 24
Population: 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 analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the PAS | Month 12 | 57.74 percentage of participants |
| Placebo + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the PAS | Month 24 | 27.68 percentage of participants |
| Tiragolumab + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the PAS | Month 12 | 54.00 percentage of participants |
| Tiragolumab + Atezolizumab | Overall Survival Rates at 12 Months and 24 Months in the PAS | Month 24 | 19.56 percentage of participants |
Comparison: Month 12p-value: 0.45895% CI: [-13.6, 6.13]Z-test
Comparison: Month 24p-value: 0.099995% CI: [-17.8, 1.55]Z-test
Secondary
Percentage of Participants With Adverse Events
An adverse event is any untoward medical occurrence in a subject 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. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Up to 65 months
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: 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.
Time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | PFS in the FAS | 5.42 months |
| Tiragolumab + Atezolizumab | PFS in the FAS | 5.06 months |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.44495% CI: [0.89, 1.31]Log Rank
Secondary
Time to Confirmed Deterioration (TTCD) of European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Physical Functioning in the PAS
TTCD was the time from randomization until the first confirmed clinically meaningful deterioration in physical functioning. TTCD was determined based on patient-reported physical functioning (items 1-5) as collected and measured by the EORTC QLQ-C30. The PF is measured on 4-point scale (1='Not at all' to 4='Very much'). A high score for the physical function 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 physical functioning 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.
Time frame: From randomization until the first confirmed clinically meaningful deterioration up to approximately 24 months
Population: PAS: All randomized participants without presence or history of brain metastases at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | Time to Confirmed Deterioration (TTCD) of European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Physical Functioning in the PAS | 19.35 months |
| Tiragolumab + Atezolizumab | Time to Confirmed Deterioration (TTCD) of European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Physical Functioning in the PAS | 15.67 months |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.981995% CI: [0.68, 1.48]Log Rank
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 global health status (GHS)/ quality of life (QoL). TTCD was determined based on patient-reported GHS/QoL (items 29-30) as collected and measured by the EORTC QLQ-C30. HS/ QoL items are scored on a 7-point scale that ranges from very poor to excellent. A high score for the GHS/QoL subscale represented a high health related quality of life. 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.
Time frame: From randomization until the first confirmed clinically meaningful deterioration up to 24 months
Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | TTCD of EORTC QLQ-C30 GHS/QoL in the FAS | NA months |
| Tiragolumab + Atezolizumab | TTCD of EORTC QLQ-C30 GHS/QoL in the FAS | NA months |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.168195% CI: [0.9, 1.84]Log Rank
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 global health status (GHS)/ quality of life (QoL). TTCD was determined based on patient-reported GHS/QoL (items 29-30) as collected and measured by the EORTC QLQ-C30. HS/QoL items are scored on a 7-point scale that ranges from very poor to excellent. A high score for the GHS/QoL subscale represented a high health related quality of life. 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.
Time frame: From randomization until the first confirmed clinically meaningful deterioration up to approximately 24 months
Population: PAS: All randomized participants without presence or history of brain metastases at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | TTCD of EORTC QLQ-C30 Global Health Status (GHS)/Quality of Life (QoL) in the PAS | NA months |
| Tiragolumab + Atezolizumab | TTCD of EORTC QLQ-C30 Global Health Status (GHS)/Quality of Life (QoL) in the PAS | NA months |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.361495% CI: [0.81, 1.79]Log Rank
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 physical functioning. TTCD was determined based on patient-reported physical functioning (items 1-5) as collected and measured by the EORTC QLQ-C30. The PF is measured on 4-point scale (1='Not at all' to 4='Very much'). A high score for the physical function 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 physical functioning 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.
Time frame: From randomization until the first confirmed clinically meaningful deterioration up to approximately 24 months
Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | TTCD of EORTC QLQ-C30 Physical Functioning in the FAS | 19.35 months |
| Tiragolumab + Atezolizumab | TTCD of EORTC QLQ-C30 Physical Functioning in the FAS | 15.67 months |
Comparison: Stratification factors were LDH (\> ULN vs. \</= ULN) and ECOG (0 vs. 1).p-value: 0.512295% CI: [0.81, 1.55]Log Rank