A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer

PFS as Determined by the Independent Review Facility (IRF)

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1 criteria, 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), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.

Time frame: From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=1%

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1 criteria, 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), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.

Time frame: From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=50%

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria, 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), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.

Time frame: From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

OS in Participants With PD-L1 Expression at TPS/TC >=1%

OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.

Time frame: From randomization to death from any cause (up to approximately 40 months)

OS in Participants With PD-L1 Expression at TPS/TC >= 50%

OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.

Time frame: From randomization to death from any cause (up to approximately 40 months)

PFS Rate at Month 6 and Month 12

PFS at 6 months and 12 months was defined as the percentage of participants who have not experienced PD as determined by the investigator according to RECIST v1.1 or death from any cause at 6 months and at 12 months, respectively. 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), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions.

Time frame: At Month 6 and Month 12

OS Rate at Month 12 and Month 24

OS rate at 12 months and 24 months was defined as the percentage of participants who have not experienced death from any cause at 12 and 24 months, respectively.

Time frame: At Month 12 and Month 24

Duration of Response (DOR)

DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Complete response (CR) was defined as the disappearance of all target and non-target lesions. 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 SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Partial response (PR) 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.

Time frame: Up to approximately 40 months

Objective Response Rate (ORR)

ORR was defined as a percentage of participants with a CR or 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. 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. Percentages have been rounded off.

Time frame: Up to approximately 40 months

Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning (PF) as Measured by European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC-QLQ-C30)

EORTC QLQ-C30=self-reported measure, with 30 questions assessing 5 aspects of subjects functioning (physical, emotional, role, cognitive \& social), 3 symptom scales (fatigue, nausea \& vomiting, \& pain), global health status (GHS) \& Quality of Life (QoL), \& 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties) within the previous week. Functioning \& symptoms items were scored on a 4-point scale: 1=not at all to 4=very much. Scores were linearly transformed to a range of 0 to 100, with higher scores reflecting better functioning. TTCD was defined time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration was defined as score decrease of ≥10 from baseline in PF scale score that were held for at least two consecutive assessments or an initial ≥10 decrease from baseline followed by death from any cause within 3 weeks.

Time frame: Up to approximately 40 months

TTCD in Participant-Reported Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30

EORTC QLQ-C30=self-reported measure, with 30 questions assessing 5 aspects of subjects functioning (physical, emotional, role, cognitive \& social), 3 symptom scales (fatigue, nausea \& vomiting, \& pain), global health status (GHS) \& Quality of Life (QoL), \& 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties) within the previous week . GHS and QoL items were scored on a 7-point scale (1=very poor 7=excellent). Scores were linearly transformed to a range of 0 to 100, with higher scores reflecting better GHS/QoL. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration was defined as score decrease of ≥10 from baseline in GHS/QoL scale score that were held for at least two consecutive assessments or an initial ≥10 decrease from baseline followed by death from any cause within 3 weeks.

Time frame: Up to approximately 40 months

TTCD in Participant-Reported Dyspnoea as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13)

The EORTC QLQ-LC13 is comprised of 13 lung cancer-specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Symptoms were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of dyspnoea. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.

Time frame: Up to approximately 40 months

TTCD in Participant-Reported Chest Pain, as Measured by EORTC QLQ-LC13

The EORTC QLQ-LC13 is comprised of 13 lung cancer-specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Chest pain were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of chest pain. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.

Time frame: Up to approximately 40 months

TTCD in Participant-Reported Cough, as Measured by EORTC QLQ-LC13

The EORTC QLQ-LC13 is comprised of 13 lung cancer-specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Cough were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of cough. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.

Time frame: Up to approximately 40 months

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 AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Time frame: From study start up to 90 days after last dose (up to approximately 40.8 months)

Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46)

The EORTC IL46 is a validated single-item question that assesses overall side effect impact, i.e. "To what extent have you been troubled with side-effects from your treatment ". Each item is scored on a 4-point scale (1= Not at all, 2= A Little, 3= Quite a Bit, and 4= Very Much).

Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57 and treatment discontinuation visit (each cycle=21 days) (Up to 40 months)

Serum Concentration of Atezolizumab

Time frame: Predose Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at treatment completion (TC)/early discontinuation (ED); and 0.5 hour (h) postdose Day 1 of Cycle 1 (each cycle=21 days) (Up to 40 months)

Serum Concentration of Tiragolumab

Time frame: Predose Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at TC/ED; and 0.5 hour (h) postdose Day 1 of Cycle 1 (each cycle=21 days) (Up to 40 months)

Number of Participants With Treatment-Emergent Anti-drug Antibodies (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 40 months

Number of Participants With Treatment-Emergent 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 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 40 months