A Study to Investigate Atezolizumab Subcutaneous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab

Time frame: Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)

Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab

Time frame: Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)

Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab

Time frame: Predose and up to 21 days post dose in Cycle 1 for cohorts 1 and 3 and from predose up to 14 days post last dose in Cycle 1 for cohort 2 (Cycle length= 21 days for cohorts 1 and 3 and 14 days for cohort 2)

Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration

Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2. Day=D; Cycle=C.

Time frame: Cohort 1: Predose: D1 & postdose: D1, 3, 8 of C1; Cohort 2: Pre & postdose: D1 of C1, 3 & postdose: D3, 8 of C1, Predose: D1 of C2; Cohort 3: Pre & postdose: D1 of C1, 2 & postdose: D3, 8 of C1, D2, 4 & 9 of C2 & pre dose: D1 of C3

Part 1: Percentage of Participants With Adverse Events (AEs)

An AE was 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 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 AEs. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 5.0 (NCI-CTCAE, v5.0). Percentages have been rounded to one decimal place.

Time frame: From initiation of study treatment up to approximately 69 months

Part 2: Percentage of Participants With AEs

An AE was 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 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 AEs. AEs were reported based on the NCI-CTCAE, V5.0. Percentages have been rounded to one decimal place.

Time frame: From initiation of study treatment up to approximately 44.7 months

Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1

Time frame: Cycle 1 (Cycle length=21 days)

Part 2: Model Predicted Ctrough at Steady State (Ctrough,ss) of Atezolizumab

1 cycle=21 days Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo.

Time frame: Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months)

Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab

1 cycle=21 days Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo

Time frame: Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months)

Part 2: Objective Response Rate (ORR)

ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1). CR was defined as the disappearance of all target lesions and any pathological lymph nodes must have 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. Percentage of participants who achieved confirmed objective response (CR or PR) have been reported. Percentages have been rounded to one decimal place.

Time frame: Up to approximately 25 months

Part 2: Progression-free Survival (PFS)

PFS was defined as the time from study start to the first occurrence of PD, as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs 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. PFS was analyzed using the Kaplan-Meier method.

Time frame: Up to approximately 25 months

Part 2: Overall Survival (OS)

OS was defined as the time from the date of study randomization to the date of death from any cause.

Time frame: Up to approximately 44.7 months

Part 2: Duration of Response (DOR)

DOR was defined as the time from first occurrence of a documented confirmed objective response (CR or PR) to PD as determined by the investigator according to RECIST v1.1. or death from any cause, whichever occurs first. CR was defined as the disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of 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). In addition to the relative increase of 20%, the SODs must also demonstrate an absolute increase of ≥ 5 mm.

Time frame: Up to approximately 25 months

Part 2: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL) 57 Physical Functioning Score

EORTC IL57 questionnaire has 10 items and covers 3 scales: physical functioning (PF), role functioning (RF) \& global health status/quality of life (GHS/QoL) \& 1 item from EORTC IL. PF scale has 5 items evaluating the extent to which participants have trouble doing strenuous activities; taking long walks \& short walks; need to stay in bed or a chair; need help with eating, dressing, bathing/using toilet. RF scale has 2 items evaluating extent to which participants are limited in doing work \& pursuing leisure activities in previous week. GHS/QoL scale has 2 items evaluating participants' overall health \& QoL in previous week. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for physical and role functioning \& a 7-point scale (where 1="Very poor" to 7="Excellent") for GHS/QoL. For each scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 = best possible score. Higher score indicates better outcome.

Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 months)

Part 2: Change From Baseline in EORTC IL57 Role Functioning Score

EORTC IL57 questionnaire has 10 items and covers 3 scales: PF, RF \& GHS/QoL \& 1 item from EORTC IL. PF scale has 5 items evaluating the extent to which participants have trouble doing strenuous activities; taking long walks \& short walks; need to stay in bed or a chair; need help with eating, dressing, bathing/using toilet. RF scale has 2 items evaluating extent to which participants are limited in doing work \& pursuing leisure activities in previous week. GHS/QoL scale has 2 items evaluating participants' overall health \& QoL in previous week. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for physical and role functioning \& a 7-point scale (where 1="Very poor" to 7="Excellent") for GHS/QoL. For each scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 = best possible score. Higher score indicates better outcome.

Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 months)

Part 2: Change From Baseline in EORTC IL57 Global Health Status Score

EORTC IL57 questionnaire has 10 items and covers 3 scales: PF, RF \& GHS/QoL \& 1 item from EORTC IL. PF scale has 5 items evaluating the extent to which participants have trouble doing strenuous activities; taking long walks \& short walks; need to stay in bed or a chair; need help with eating, dressing, bathing/using toilet. RF scale has 2 items evaluating extent to which participants are limited in doing work \& pursuing leisure activities in previous week. GHS/QoL scale has 2 items evaluating participants' overall health \& QoL in previous week. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for physical and role functioning \& a 7-point scale (where 1="Very poor" to 7="Excellent") for GHS/QoL. For each scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 = best possible score. Higher score indicates better outcome.

Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 months)

Part 2: Overall Satisfaction With Treatment Over Time, Assessed by the Modified Satisfaction With Therapy (SWT) Scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ)

Modified SWT scale of the CTSQ consisted of seven items that measured seven domains related to satisfaction with cancer therapy. These include worthwhile, difficulty, benefits, feelings about side effects, form of therapy, overall satisfaction, and if participants would choose the therapy taking everything into consideration. Each domain is rated on a 5-point scale, with 1 representing the worst response and 5 representing the best response, except in the case of one reverse-scored item. Mean of the items were linearly transformed to obtain scores from 0-100, where 100 was the best possible score. Higher scores indicate higher satisfaction. Here, data for 'overall satisfaction' domain has been presented.

Time frame: Day 1 Cycle 3 or Treatment Discontinuation Visit (if treatment discontinued at any visit before Cycle 3) (Cycle length = 21 days)

Part 2: Percentage of Participants by Their Responses to AE's Burden Over Time, Assessed by the Treatment-related Symptom Burden Item From the EORTC IL57

The overall patient-reported AE burden was assessed using a single item from the EORTC IL57 questionnaire i.e "To what extent have you been troubled with side-effects from your treatment?" The questions were answered on a 4-point Likert scale, where 1="Not at all" to 4="Very much". Higher scores indicated greater AE burden. Percentages have been rounded to one decimal place.

Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, and 64 (Cycle length = 21 days)

Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration

The percentage of ADA-positive participants after atezolizumab administration was reported. 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). Percentages have been rounded to one decimal place.

Time frame: From Cycle 1 Day 1 (Cycle length = 21 days) up to treatment discontinuation visit (Up to approximately 20 months)

Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration

The percentage of ADA-positive participants after atezolizumab SC formulated with rHuPH20 administration was reported. Participants who received atezolizumab SC formulated with rHuPH20 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 rHuPH20 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). Percentages have been rounded to one decimal place.

Time frame: From Cycle 1 Day 1 (Cycle length = 21 days) up to treatment discontinuation visit (Up to approximately 20 months)

Part 2: Percentage of Health Care Professionals (HCPs) by Their Response to Question 2 of HCP SC Versus IV Perspective Questionnaire

The HCP SC versus IV Perspective Questionnaire consisted of five items evaluating the number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as an IV infusion and as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 2 is being reported here: Question 2: Which formulation of atezolizumab (SC or IV) do you think is more convenient for you? Responses to this question are reported in the data table. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'first participant in \[FPI\]' date to 'last participant last visit \[LPLV\]' for Part 2).

Time frame: After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 48 months)

Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Versus IV Perspective Questionnaire

The HCP SC versus IV Perspective Questionnaire consisted of five items evaluating the number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as an IV infusion and as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 3 is being reported here: Question 3: If used in routine practice, do you think administering atezolizumab SC could save staff time compared to atezolizumab IV? The responses to this question could be Yes; No; Unsure. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2).

Time frame: After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 48 months)

Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Versus IV Perspective Questionnaire

The HCP SC versus IV Perspective Questionnaire consisted of five items evaluating the number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as an IV infusion and as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 4 is being reported here: Question 4: Overall, were you more satisfied with atezolizumab SC or atezolizumab IV? The responses included: More satisfied with atezolizumab SC; Equally satisfied with both formulations; More satisfied with atezolizumab IV. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2).

Time frame: After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 48 months)

Part 2: Percentage of HCPs by Their Response to Question 2 of the HCP SC Perspective Questionnaire

The HCP SC Perspective Questionnaire consisted of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 2 is being reported here: Question 2: Do you think atezolizumab SC is convenient? The responses to this question could be: Yes; No; and Unsure. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Percentages have been rounded to one decimal place.

Time frame: After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 48 months)

Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Perspective Questionnaire

The HCP SC Perspective Questionnaire consisted of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 3 is being reported here: Question 3: Overall, how easy did you find atezolizumab SC administration? The responses to this question could be: Very easy; Fairly easy; Not at all easy. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Percentages have been rounded to one decimal place.

Time frame: After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 48 months)

Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Perspective Questionnaire

The HCP SC Perspective Questionnaire consisted of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 4 is being reported here: Question 4: Overall, how satisfied were you with atezolizumab SC? The responses to this question could be: Very satisfied; Satisfied; Dissatisfied; Very dissatisfied. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Percentages have been rounded to one decimal place.

Time frame: After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 48 months)