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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
135
Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.
Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Objective Response Rate (ORR)
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.
Time frame: From baseline until a total of 80 progression-free survival (PFS) events have occurred (up to approximately 11 months)
Progression-free Survival (PFS)
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.
Time frame: From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)
Duration of Objective Response (DOR)
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.
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Arizona Oncology Associates, PC - HAL
Tempe, Arizona, United States
SCRI Florida Cancer Specialists South
Fort Myers, Florida, United States
Florida Cancer Specialists - NORTH - SCRI - PPDS
St. Petersburg, Florida, United States
Illinois Cancer Specialists
Arlington Heights, Illinois, United States
Illinois Cancer Care
Peoria, Illinois, United States
University of Kansas Medical Center
Westwood, Kansas, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Research Medical Center
Kansas City, Missouri, United States
SCRI Tennessee Oncology
Nashville, Tennessee, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, United States
...and 30 more locations
Time frame: Up to approximately 36 months
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.
Time frame: Up to approximately 36 months
Number of Participants With Adverse Events (AEs)
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.
Time frame: From initiation of study drug up to approximately 83.7 months
Minimum Serum Concentration (Cmin) of Tiragolumab
Time frame: Predose on Day 1 of Cycles 1, 3 and 11 (Cycle length = 21 days)
Cmin of Atezolizumab
Time frame: 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
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.
Time frame: Up to approximately 36 months
Number of Participants With Treatment-Emergent ADAs to Atezolizumab
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.
Time frame: Up to approximately 36 months