Non-small Cell Lung Cancer
Conditions
Brief summary
This study will evaluate the safety and efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in chemotherapy-naive patients with locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), excluding patients with a sensitizing EGFR mutation or ALK translocation.
Interventions
DRUGAtezolizumab
Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.
DRUGTiragolumab
Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
DRUGPlacebo
Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ECOG Performance Status of 0 or 1 * Histologically or cytologically documented locally advanced unresectable NSCLC, recurrent, or metastatic NSCLC of either squamous or non-squamous histology * No prior systemic treatment for locally advanced unresectable or metastatic NSCLC * Tumor PD-L1 expression * Measurable disease, as defined by RECIST v1.1 * Life expectancy \>=12 weeks * Adequate hematologic and end-organ function * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
Exclusion criteria
Cancer-Specific Exclusions: * Patients with NSCLC known to have a sensitizing mutation in the EGFR gene or an ALK fusion oncogene * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>=2 weeks prior to screening * History of leptomeningeal disease * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures * Uncontrolled tumor-related pain * Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab * Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome General Medical Exclusions: * Pregnant and lactating women * Significant cardiovascular disease * Severe infections within 4 weeks prior to randomization * Major surgical procedure other than for diagnosis within 4 weeks prior to randomization Treatment-Specific Exclusions: * History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation * History of autoimmune disease * Prior allogeneic bone marrow transplantation or solid organ transplantation * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan * Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or active tuberculosis * Administration of a live, attenuated vaccine within 4 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From baseline until a total of 80 progression-free survival (PFS) events have occurred (up to approximately 11 months) | ORR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off. |
| Progression-free Survival (PFS) | From baseline until a total of 80 PFS events have occurred (up to approximately 11 months) | PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to 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 at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. Kaplan-Meier (KM) methodology was used to estimate the median PFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Objective Response (DOR) | Up to approximately 36 months | DOR was defined as the time from the first occurrence of a documented objective response (OR) (CR or PR) to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target lesions) must have a 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 at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. KM methodology was used to estimate the median DOR. |
| Overall Survival (OS) | Up to approximately 36 months | OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS. |
| Number of Participants With Adverse Events (AEs) | From initiation of study drug up to approximately 83.7 months | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Minimum Serum Concentration (Cmin) of Tiragolumab | Predose on Day 1 of Cycles 1, 3 and 11 (Cycle length = 21 days) | — |
| Cmin of Atezolizumab | Predose on Day 1 of Cycles 1, 3 and 11 (Cycle length = 21 days) | — |
| Number of Participants With Treatment-Emergent Anti-drug Antibodies (ADAs) to Tiragolumab | Up to approximately 36 months | Participants who received tiragolumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here. |
| Number of Participants With Treatment-Emergent ADAs to Atezolizumab | Up to approximately 36 months | Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here. |
Countries
France, Serbia, South Korea, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 135 participants with previously untreated, locally advanced, unresectable, or metastatic programmed death-ligand 1 (PD-L1)-selected non-small cell lung cancer (NSCLC) took part in the study at 39 investigative sites across 6 countries from 08 Aug 2018 to 14 Nov 2025.
Pre-assignment details
Participants were randomized in a 1:1 ratio to receive either tiragolumab plus atezolizumab or placebo plus atezolizumab. The study is considered "Completed" because all the pre-planned study activities and analyses have been performed.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Atezolizumab Participants received atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle. | 68 |
| Tiragolumab + Atezolizumab Participants received atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle. | 67 |
| Total | 135 |
Baseline characteristics
| Characteristic | Tiragolumab + Atezolizumab | Total | Placebo + Atezolizumab |
|---|---|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 10.4 | 66.4 years STANDARD_DEVIATION 10.1 | 67.0 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 123 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 41 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) White | 42 Participants | 82 Participants | 40 Participants |
| Sex: Female, Male Female | 28 Participants | 48 Participants | 20 Participants |
| Sex: Female, Male Male | 39 Participants | 87 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 57 / 68 | 51 / 67 |
| other Total, other adverse events | 59 / 68 | 63 / 67 |
| serious Total, serious adverse events | 28 / 68 | 40 / 67 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR, defined as a complete response (CR) or partial response (PR) on two consecutive occasions \>/=4 weeks apart, as determined by the investigator according to RECIST v1.1. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Time frame: From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months)
Population: Intent-to-Treat (ITT) population included all participants randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Atezolizumab | Objective Response Rate (ORR) | 16.2 percentage of participants |
| Tiragolumab + Atezolizumab | Objective Response Rate (ORR) | 31.3 percentage of participants |
Comparison: Stratified analysis based on PD-L1 immunohistochemistry (IHC) 22C3 pharmDx, tumor histology status, and tobacco history.95% CI: [1.07, 6.14]
Primary
Progression Free Survival (PFS)
PFS, defined as the time from randomization to the first occurrence of disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
Time frame: From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Atezolizumab | Progression Free Survival (PFS) | 3.58 months |
| Tiragolumab + Atezolizumab | Progression Free Survival (PFS) | 5.42 months |
Comparison: Stratified analysis based on PD-L1 IHC 22C3 pharmDx, tumor histology status, and tobacco history.95% CI: [0.37, 0.9]
Secondary
Duration of Objective Response (DOR)
DOR, defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
Time frame: Up to 6 years
Secondary
Overall Survival (OS)
OS, defined as the time from randomization to death from any cause.
Time frame: Up to 6 years
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 6 years
Secondary
Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days)
Secondary
Serum Concentrations of Atezolizumab
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days)
Secondary
Serum Concentrations of Tiragolumab
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days)