IMpower133: A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02763579
• Collaborator: (none)
• Enrollment: 403
• Locations: 114
• Arms: 2
• Anticipated Duration (Months): 73
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized, Phase I/III, multicenter, double-blinded, placebo-controlled study was designed to evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin plus (+) etoposide compared with treatment with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC. Participants will be randomized in a 1:1 ratio to receive either atezolizumab + carboplatin + etoposide or placebo + carboplatin + etoposide on 21-day cycles for four cycles in the induction phase followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or symptomatic deterioration.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Carcinoma	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Carboplatin; Drug: Etoposide; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 403 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase I/III, Randomized, Double-Blind, Placebo-Controlled Study of Carboplatin Plus Etoposide With or Without Atezolizumab (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
• Actual Study Start Date: Jun 7, 2016
• Actual Primary Completion Date: Apr 24, 2018
• Anticipated Study Completion Date: Jul 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atezolizumab + Carboplatin + Etoposide Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).; Other Names: MPDL3280A, RO5541267, Tecentriq ; Drug: Carboplatin; Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).; Drug: Etoposide; Etoposide intravenous infusion was administered at a dose of 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).
Active Comparator: Placebo + Carboplatin + Etoposide Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Drug: Carboplatin; Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).; Drug: Etoposide; Etoposide intravenous infusion was administered at a dose of 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).; Drug: Placebo; Placebo intravenous infusion was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Outcome Measures

Primary Outcome Measures

1. Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 [Baseline until PD or death, whichever occurs first (up to approximately 23 months)]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).

2. Duration of Overall Survival (OS) [Baseline until death from any cause (up to approximately 23 months)]

Secondary Outcome Measures

1. Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1 [Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 46 months)]

2. Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 [First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 46 months)]

3. Percentage of Participants Alive and Without PD, as Assessed by the Investigator Using RECIST v1.1, at 6 Months and 1 Year [6 months, 1 year (up to approximately 46 months)]

4. Percentage of Participants Alive at 1 Year and 2 Years [1 year, 2 years (up to approximately 46 months)]

5. Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) Score [Baseline until deterioration per symptom subscale (up to approximately 46 months)]

6. TTD Per EORTC QLQ Lung Cancer Module (LC13) Score [Baseline until deterioration per symptom subscale (up to approximately 46 months)]

7. Percentage of Participants With Adverse Events [Baseline until up to 90 days after end of treatment (up to approximately 46 months)]

8. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) [Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)]

9. Maximum Observed Serum Concentration (Cmax) of Atezolizumab [Predose (0 H) and postdose (0.5 H) on D1 of C1; predose (0 H) on D1 of C2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)]

   Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.

10. Minimum Observed Serum Concentration (Cmin) of Atezolizumab [Predose (0 H) on D1 of C1, 2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)]

    Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.

11. Plasma Concentration of Carboplatin [Predose (0 H) and 5-10 minutes before end/1 H after end of carboplatin infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months)]

12. Plasma Concentration of Etoposide [Predose (0 H) and 5-10 minutes before end/1 H and 4H after end of etoposide infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system)

• No prior systemic treatment for ES-SCLC

• Eastern Cooperative Oncology Group performance status of 0 or 1

• Measurable disease, as defined by 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:

• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation

• Malignancies other than 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

• Pregnant or lactating women

• History of autoimmune disease

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

• Positive test result for human immunodeficiency virus (HIV)

• Active hepatitis B or hepatitis C

• Severe infections at the time of randomization

• Significant cardiovascular disease

• Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic antibody

• History of severe (or known) hypersensitivity to chimeric or humanized antibodies or fusion proteins or any component of atezolizumab formulation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists - Fort Myers (Broadway)	Fort Myers	Florida	United States	33901
2	Florida Hospital	Orlando	Florida	United States	32804
3	Florida Cancer Specialists.	Saint Petersburg	Florida	United States	33705
4	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia	United States	30060
5	Rush University Medical Center	Chicago	Illinois	United States	60612-3244
6	Illinois Cancer Care	Peoria	Illinois	United States	61615
7	Cancer Treatment Centers of America - Midwestern Regional Medical Center	Zion	Illinois	United States	60099
8	Louisville Oncology	Louisville	Kentucky	United States	40202
9	New England Cancer Specialists	Scarborough	Maine	United States	04074
10	Weinberg CA Inst Franklin Sq	Baltimore	Maryland	United States	21237
11	Mayo Clinic	Rochester	Minnesota	United States	55905
12	Comprehensive Cancer Centers of Nevada - Eastern Avenue	Las Vegas	Nevada	United States	89169
13	The Valley Hospital	Paramus	New Jersey	United States	07652
14	Broome Oncology - Binghamton	Binghamton	New York	United States	13905
15	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
16	Tennessee Oncology Chattanooga	Chattanooga	Tennessee	United States	37404
17	Tennessee Oncology PLLC - Nashville (20th Ave)	Nashville	Tennessee	United States	37203
18	Vanderbilt Medical Center	Nashville	Tennessee	United States	37232-7610
19	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
20	Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
21	Northwest Medical Specialties	Tacoma	Washington	United States	98405
22	University of Wisconsin	Madison	Wisconsin	United States	53792
23	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
24	The Prince Charles Hospital; Oncology Dept.	Chermside	Queensland	Australia	4032
25	Royal Melbourne Hospital; Hematology and Medical Oncology	Parkville	Victoria	Australia	3052
26	Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten	Linz		Austria	4020
27	Salzburger Landeskliniken; Universitätsklinik für Pneumologie/ Lungenheilkunde	Salzburg		Austria	5020
28	SMZ - Baumgartner Hohe, Otto-Wagner-Spital; 2.Interne Lungenabteilung	Wien		Austria	1140
29	Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie	Wien		Austria	1210
30	Santa Casa de Misericordia de Salvador	Salvador	BA	Brazil	40050-410
31	Hospital Bruno Born	Lajeado	RS	Brazil	95900-000
32	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil	90035-903
33	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP	Brazil	01246-000
34	Bradford Hill Centro de Investigaciones Clinicas; Bradford Hill Centro de Investigaciones Clinicas	Recoleta		Chile	8420383
35	OrlandiOncología	Santiago		Chile	7500713
36	Beijing Cancer Hospital	Beijing		China	100142
37	Jilin Cancer Hospital	Changchun		China	132013
38	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou		China	510120
39	Harbin Medical University Cancer Hospital	Harbin		China	150081
40	Jiangsu Cancer Hospital	Nanjing City		China	211100
41	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
42	Zhongshan Hospital Fudan University	Shanghai		China	200032
43	Zhejiang Cancer Hospital	Zhejiang		China	310022
44	Henan Cancer Hospital	Zhengzhou		China	450008
45	Fakultni nemocnice Olomouc	Olomouc		Czechia	775 20
46	Thomayerova nemocnice	Praha 4 - Krc		Czechia	140 59
47	Fakultni nemocnice Na Bulovce	Praha 8		Czechia	180 81
48	Institut Bergonie; Oncologie	Bordeaux		France	33076
49	Centre Francois Baclesse; Oncologie	Caen		France	14076
50	Hopital Calmette; Pneumologie Oncologie Ouest	Lille		France	59037
51	Hôpital Nord - AP-HM Marseille#	Marseille		France	13915
52	Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie	Gauting		Germany	82131
53	LungenClinic Großhansdorf GmbH	Großhansdorf		Germany	22927
54	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II	Halle		Germany	06120
55	Thoraxklinik Heidelberg gGmbH	Heidelberg		Germany	69126
56	Fachklinik für Lungenerkrankungen	Immenhausen		Germany	34376
57	Sotiria Chest Hospital of Athens	Athens		Greece	11527
58	Agioi Anargyroi; 3Rd Dept. of Medical Oncology	Athens		Greece	145 64
59	University Hospital of Patras Medical Oncology	Patras		Greece	265 04
60	Semmelweis Egyetem, AOK, Pulmonologiai Klinika	Budapest		Hungary	1083
61	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest		Hungary	1121
62	Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika	Debrecen		Hungary	4032
63	Tudogyogyintezet Torokbalint	Torokbalint		Hungary	2045
64	A.O. Universitaria Di Parma	Parma	Emilia-Romagna	Italy	43100
65	Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica	Roma	Lazio	Italy	00128
66	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia	Italy	20133
67	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia	Italy	20141
68	IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia	San Giovanni Rotondo	Puglia	Italy	71013
69	Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare	Pisa	Toscana	Italy	56124
70	Kyushu University Hospital; Respiratory	Fukuoka		Japan	812-8582
71	National Hospital Organization Himeji Medical Center	Hyogo		Japan	670-8520
72	Kanagawa Cancer Center;Thoracic Oncology	Kanagawa		Japan	241-8515
73	University Hospital Kyoto Prefectural University of Medicine, Pulmonary Medicine	Kyoto		Japan	602-8566
74	Sendai Kousei Hospital; Pulmonary Medicine	Miyagi		Japan	980-0873
75	Kurashiki Central Hospital; Respiratory Medicine	Okayama		Japan	710-8602
76	Kindai University Hospital; Medical Oncology	Osaka		Japan	589-8511
77	National Hospital Organization Kinki-Chuo Chest Medical Center; Internal Medicine	Osaka		Japan	591-8555
78	Saitama Cancer Center; Thoracic Oncology	Satima		Japan	362-0806
79	Shizuoka Cancer Center; Thoracic Oncology	Shizuoka		Japan	411-8777
80	Tokyo Metropolitan Komagome Hospital; Thoracic Oncology and Respiratory Medicine	Tokyo		Japan	113-8677
81	The Cancer Institute Hospital of JFCR, Respiratory Medicine	Tokyo		Japan	135-8550
82	Wakayama Medical University Hospital; Respiratory Medicine and Medical Oncology	Wakayama		Japan	641-8509
83	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
84	Seoul National University Hospital	Seoul		Korea, Republic of	03080
85	Asan Medical Center	Seoul		Korea, Republic of	05505
86	Samsung Medical Center	Seoul		Korea, Republic of	06351
87	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)	Mexico	03100
88	Medical University of Gdansk	Gdansk		Poland	80-952
89	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz		Poland	93-513
90	Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc; Oddzial V Chemioterapii Nowotworow Pluc	Olsztyn		Poland	10-357
91	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy	Otwock		Poland	05-400
92	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu	Poznan		Poland	60-569
93	Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology	Warszawa		Poland	02-781
94	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast	Russian Federation	143423
95	N.N.Burdenko Main Military Clinical Hospital; Oncology Dept	Moscow		Russian Federation	105229
96	Russian Oncology Research Center n.a. N.N. Blokhin	Moscow		Russian Federation	115478
97	City Clinical Hospital No. 1	Novosibirsk		Russian Federation	630047
98	City Clinical Onc.	Saint-Petersburg		Russian Federation	198255
99	Scientific Research Oncology Institute named after N.N. Petrov; Oncology	St. Petersburg		Russian Federation	197758
100	Clinical Center of Serbia	Belgrade		Serbia	11000
101	Clinical Center Nis; Clinic for pulmonary diseases	Nis		Serbia	18 000
102	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
103	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
104	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
105	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga		Spain	29010
106	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
107	Hosp Clinico Univ Lozano Blesa; División De Oncología Médica	Zaragoza		Spain	50009
108	National Taiwan Uni Hospital; Internal Medicine	Taipei		Taiwan	100
109	Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology	Taipei		Taiwan	112
110	Chang Gung Medical Foundation - Linkou; Chest Dept	Taoyuan		Taiwan	333
111	Royal Devon & Exeter Hospital; Oncology Centre	Exeter		United Kingdom	EX2 5DW
112	Barts and the London NHS Trust.	London		United Kingdom	EC1A 7BE
113	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London		United Kingdom	SE1 9RT
114	Christie Hospital Nhs Trust; Medical Oncology	Manchester		United Kingdom	M2O 4BX

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 6, 2019

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02763579
• Other Study ID Numbers: GO30081; 2015-004861-97
• First Posted: May 5, 2016
• Last Update Posted: Jul 18, 2022
• Last Verified: Jul 1, 2022

• Additional relevant MeSH terms: Small Cell Lung Carcinoma; Carboplatin; Etoposide; Atezolizumab; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	Participants in this study included: extensive-stage small cell lung cancer (ES-SCLC) with no prior systemic treatment for ES-SCLC.

Arm/Group Title	Atezolizumab + Carboplatin + Etoposide	Placebo + Carboplatin + Etoposide
Arm/Group Description	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Period Title: Overall Study
STARTED	201	202
COMPLETED	0	0
NOT COMPLETED	201	202

Baseline Characteristics

Arm/Group Title	Atezolizumab + Carboplatin + Etoposide	Placebo + Carboplatin + Etoposide	Total
Arm/Group Description	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Total of all reporting groups
Overall Participants	201	202	403
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (8.8)	63.6 (9.0)	63.7 (8.9)
Sex: Female, Male (Count of Participants)
Female	72 35.8%	70 34.7%	142 35.2%
Male	129 64.2%	132 65.3%	261 64.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.5%	1 0.2%
Asian	33 16.4%	36 17.8%	69 17.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.5%	2 1%	3 0.7%
White	163 81.1%	159 78.7%	322 79.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 2%	4 2%	8 2%

Outcome Measures

1. Primary Outcome

Title	Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).
Time Frame	Baseline until PD or death, whichever occurs first (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atezolizumab + Carboplatin + Etoposide	Placebo + Carboplatin + Etoposide
Arm/Group Description	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Measure Participants	201	202
Median (95% Confidence Interval) [Months]	5.2 (4.4)	4.3 (4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Carboplatin + Etoposide, Placebo + Carboplatin + Etoposide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0170
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Duration of Overall Survival (OS)
Time Frame	Baseline until death from any cause (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atezolizumab + Carboplatin + Etoposide	Placebo + Carboplatin + Etoposide
Arm/Group Description	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Measure Participants	201	202
Median (95% Confidence Interval) [Months]	12.3 (10.8)	10.3 (9.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Carboplatin + Etoposide, Placebo + Carboplatin + Etoposide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0069
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.54 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1
Time Frame	Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
Time Frame	First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Percentage of Participants Alive and Without PD, as Assessed by the Investigator Using RECIST v1.1, at 6 Months and 1 Year
Time Frame	6 months, 1 year (up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Percentage of Participants Alive at 1 Year and 2 Years
Time Frame	1 year, 2 years (up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) Score
Time Frame	Baseline until deterioration per symptom subscale (up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	TTD Per EORTC QLQ Lung Cancer Module (LC13) Score
Time Frame	Baseline until deterioration per symptom subscale (up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Time Frame	Baseline until up to 90 days after end of treatment (up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)
Time Frame	Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Description	Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.
Time Frame	Predose (0 H) and postdose (0.5 H) on D1 of C1; predose (0 H) on D1 of C2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Atezolizumab
Description	Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.
Time Frame	Predose (0 H) on D1 of C1, 2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Plasma Concentration of Carboplatin
Time Frame	Predose (0 H) and 5-10 minutes before end/1 H after end of carboplatin infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Plasma Concentration of Etoposide
Time Frame	Predose (0 H) and 5-10 minutes before end/1 H and 4H after end of etoposide infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From the first study drug administration to the data cutoff date: 24 April 2018 (up to 23 months).
Adverse Event Reporting Description	Adverse Events reporting is for the Safety Evaluable Participants. Safety Evaluable Participants is defined as patients who received any amount of any component of study treatment.
Arm/Group Title	Atezolizumab + Carboplatin + Etoposide		Placebo + Carboplatin + Etoposide
Arm/Group Description	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.		Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
All Cause Mortality
	Atezolizumab + Carboplatin + Etoposide		Placebo + Carboplatin + Etoposide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/201 (50.2%)		132/202 (65.3%)
Serious Adverse Events
	Atezolizumab + Carboplatin + Etoposide		Placebo + Carboplatin + Etoposide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/198 (37.4%)		68/196 (34.7%)
Blood and lymphatic system disorders
ANAEMIA	3/198 (1.5%)	4	2/196 (1%)	2
DISSEMINATED INTRAVASCULAR COAGULATION	0/198 (0%)	0	1/196 (0.5%)	1
FEBRILE NEUTROPENIA	5/198 (2.5%)	5	9/196 (4.6%)	9
LEUKOCYTOSIS	0/198 (0%)	0	1/196 (0.5%)	1
LEUKOPENIA	2/198 (1%)	2	1/196 (0.5%)	1
NEUTROPENIA	7/198 (3.5%)	7	8/196 (4.1%)	8
PANCYTOPENIA	0/198 (0%)	0	4/196 (2%)	4
THROMBOCYTOPENIA	5/198 (2.5%)	5	4/196 (2%)	4
Cardiac disorders
ATRIAL FIBRILLATION	1/198 (0.5%)	1	2/196 (1%)	3
ATRIOVENTRICULAR BLOCK COMPLETE	1/198 (0.5%)	1	0/196 (0%)	0
CARDIAC FAILURE	0/198 (0%)	0	1/196 (0.5%)	1
CARDIAC TAMPONADE	1/198 (0.5%)	1	0/196 (0%)	0
CARDIOPULMONARY FAILURE	0/198 (0%)	0	1/196 (0.5%)	1
PERICARDIAL EFFUSION	1/198 (0.5%)	1	1/196 (0.5%)	1
SUPRAVENTRICULAR TACHYCARDIA	0/198 (0%)	0	1/196 (0.5%)	1
Endocrine disorders
AUTOIMMUNE THYROIDITIS	2/198 (1%)	2	0/196 (0%)	0
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	0/198 (0%)	0	1/196 (0.5%)	1
Gastrointestinal disorders
ABDOMINAL ADHESIONS	1/198 (0.5%)	2	0/196 (0%)	0
ABDOMINAL PAIN	1/198 (0.5%)	1	0/196 (0%)	0
SMALL INTESTINAL OBSTRUCTION	1/198 (0.5%)	2	0/196 (0%)	0
NAUSEA	1/198 (0.5%)	1	0/196 (0%)	0
LIP OEDEMA	1/198 (0.5%)	1	0/196 (0%)	0
INTESTINAL OBSTRUCTION	1/198 (0.5%)	1	0/196 (0%)	0
ILEUS	1/198 (0.5%)	1	0/196 (0%)	0
GASTROINTESTINAL HAEMORRHAGE	0/198 (0%)	0	1/196 (0.5%)	1
GASTRITIS	1/198 (0.5%)	1	0/196 (0%)	0
FAECES DISCOLOURED	0/198 (0%)	0	1/196 (0.5%)	1
GASTRIC ULCER PERFORATION	0/198 (0%)	0	1/196 (0.5%)	1
DIVERTICULAR PERFORATION	1/198 (0.5%)	1	0/196 (0%)	0
DIARRHOEA	3/198 (1.5%)	3	1/196 (0.5%)	1
COLITIS	2/198 (1%)	2	0/196 (0%)	0
PANCREATITIS	0/198 (0%)	0	1/196 (0.5%)	3
PANCREATITIS ACUTE	1/198 (0.5%)	1	0/196 (0%)	0
PROCTITIS	1/198 (0.5%)	1	0/196 (0%)	0
AUTOIMMUNE COLITIS	1/198 (0.5%)	1	0/196 (0%)	0
VOMITING	3/198 (1.5%)	3	3/196 (1.5%)	3
General disorders
ASTHENIA	2/198 (1%)	2	1/196 (0.5%)	1
CHEST PAIN	0/74 (0%)	0	1/68 (1.5%)	1
DEATH	1/198 (0.5%)	1	0/196 (0%)	0
FATIGUE	3/198 (1.5%)	3	0/196 (0%)	0
GENERAL PHYSICAL HEALTH DETERIORATION	2/198 (1%)	2	1/196 (0.5%)	1
NON-CARDIAC CHEST PAIN	0/198 (0%)	0	1/196 (0.5%)	1
PYREXIA	2/198 (1%)	2	0/196 (0%)	0
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	0/198 (0%)	0	1/196 (0.5%)	1
Hepatobiliary disorders
CHOLANGITIS	1/198 (0.5%)	1	0/196 (0%)	0
JAUNDICE	1/198 (0.5%)	2	0/196 (0%)	0
Infections and infestations
BRONCHITIS	2/198 (1%)	2	0/196 (0%)	0
CLOSTRIDIUM DIFFICILE COLITIS	1/198 (0.5%)	1	0/196 (0%)	0
CLOSTRIDIUM DIFFICILE INFECTION	0/198 (0%)	0	1/196 (0.5%)	1
CYTOMEGALOVIRUS INFECTION	1/198 (0.5%)	1	0/196 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	2/198 (1%)	2	0/196 (0%)	0
LUNG ABSCESS	0/198 (0%)	0	1/196 (0.5%)	1
LUNG INFECTION	0/198 (0%)	0	3/196 (1.5%)	3
NEUTROPENIC SEPSIS	0/198 (0%)	0	1/196 (0.5%)	1
PNEUMONIA	9/198 (4.5%)	12	7/196 (3.6%)	8
PULMONARY SEPSIS	0/198 (0%)	0	1/196 (0.5%)	1
PYOPNEUMOTHORAX	0/198 (0%)	0	1/196 (0.5%)	1
RESPIRATORY TRACT INFECTION	1/198 (0.5%)	1	1/196 (0.5%)	1
SEPSIS	0/198 (0%)	0	1/196 (0.5%)	1
SEPTIC SHOCK	0/198 (0%)	0	1/196 (0.5%)	1
UPPER RESPIRATORY TRACT INFECTION	0/198 (0%)	0	1/196 (0.5%)	1
URINARY TRACT INFECTION	2/198 (1%)	2	2/196 (1%)	2
Injury, poisoning and procedural complications
FEMUR FRACTURE	1/198 (0.5%)	1	1/196 (0.5%)	1
HEAD INJURY	1/198 (0.5%)	1	0/196 (0%)	0
INFUSION RELATED REACTION	1/198 (0.5%)	1	2/196 (1%)	2
RADIATION OESOPHAGITIS	0/198 (0%)	0	1/196 (0.5%)	1
THORACIC VERTEBRAL FRACTURE	0/198 (0%)	0	1/196 (0.5%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/198 (0.5%)	1	1/196 (0.5%)	1
ASPARTATE AMINOTRANSFERASE INCREASED	1/198 (0.5%)	1	1/196 (0.5%)	1
BLOOD ALKALINE PHOSPHATASE INCREASED	1/198 (0.5%)	1	0/196 (0%)	0
BLOOD CREATININE INCREASED	1/198 (0.5%)	2	0/196 (0%)	0
LIVER FUNCTION TEST INCREASED	1/198 (0.5%)	1	0/196 (0%)	0
NEUTROPHIL COUNT DECREASED	0/198 (0%)	0	1/196 (0.5%)	1
PLATELET COUNT DECREASED	0/198 (0%)	0	2/196 (1%)	2
TRANSAMINASES INCREASED	1/198 (0.5%)	1	0/196 (0%)	0
WHITE BLOOD CELL COUNT DECREASED	0/198 (0%)	0	1/196 (0.5%)	1
Metabolism and nutrition disorders
DEHYDRATION	1/198 (0.5%)	1	0/196 (0%)	0
HYPERGLYCAEMIA	2/198 (1%)	2	0/196 (0%)	0
HYPOKALAEMIA	0/198 (0%)	0	1/196 (0.5%)	1
HYPOMAGNESAEMIA	0/198 (0%)	0	1/196 (0.5%)	1
HYPONATRAEMIA	1/198 (0.5%)	1	4/196 (2%)	4
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/198 (0.5%)	1	0/196 (0%)	0
PAIN IN EXTREMITY	1/198 (0.5%)	1	0/196 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTATIC NEOPLASM	1/198 (0.5%)	1	0/196 (0%)	0
TUMOUR PAIN	0/198 (0%)	0	1/196 (0.5%)	1
Nervous system disorders
CEREBROVASCULAR ACCIDENT	0/198 (0%)	0	1/196 (0.5%)	1
GUILLAIN-BARRE SYNDROME	1/198 (0.5%)	1	0/196 (0%)	0
NEUROPATHY PERIPHERAL	1/198 (0.5%)	1	0/196 (0%)	0
SOMNOLENCE	1/198 (0.5%)	1	0/196 (0%)	0
SPINAL CORD OEDEMA	0/198 (0%)	0	1/196 (0.5%)	1
SYNCOPE	3/198 (1.5%)	3	0/196 (0%)	0
TRANSIENT ISCHAEMIC ATTACK	1/198 (0.5%)	1	0/196 (0%)	0
TRIGEMINAL NEURALGIA	1/198 (0.5%)	1	0/196 (0%)	0
Psychiatric disorders
ALCOHOL ABUSE	0/198 (0%)	0	1/196 (0.5%)	1
DEPRESSION	1/198 (0.5%)	1	0/196 (0%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY	2/198 (1%)	2	0/196 (0%)	0
TUBULOINTERSTITIAL NEPHRITIS	1/198 (0.5%)	1	0/196 (0%)	0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	0/198 (0%)	0	2/196 (1%)	2
BRONCHIAL OBSTRUCTION	1/198 (0.5%)	1	0/196 (0%)	0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	2/198 (1%)	2	2/196 (1%)	3
DYSPNOEA	1/198 (0.5%)	1	2/196 (1%)	2
HAEMOPTYSIS	2/198 (1%)	2	1/196 (0.5%)	1
HYPERCAPNIA	0/198 (0%)	0	1/196 (0.5%)	1
PLEURAL EFFUSION	2/198 (1%)	2	1/196 (0.5%)	1
PNEUMONITIS	1/198 (0.5%)	1	2/196 (1%)	2
PNEUMOTHORAX	0/198 (0%)	0	1/196 (0.5%)	1
PULMONARY EMBOLISM	0/198 (0%)	0	2/196 (1%)	2
PULMONARY OEDEMA	1/198 (0.5%)	1	0/196 (0%)	0
RESPIRATORY FAILURE	1/198 (0.5%)	1	0/196 (0%)	0
Skin and subcutaneous tissue disorders
RASH	0/198 (0%)	0	1/196 (0.5%)	1
SKIN TOXICITY	1/198 (0.5%)	1	0/196 (0%)	0
Vascular disorders
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	1/198 (0.5%)	1	0/196 (0%)	0
PERIPHERAL ARTERY OCCLUSION	0/198 (0%)	0	1/196 (0.5%)	1
SUPERIOR VENA CAVA SYNDROME	1/198 (0.5%)	1	0/196 (0%)	0
THROMBOPHLEBITIS	1/198 (0.5%)	1	0/196 (0%)	0
Other (Not Including Serious) Adverse Events
	Atezolizumab + Carboplatin + Etoposide		Placebo + Carboplatin + Etoposide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	190/198 (96%)		186/196 (94.9%)
Blood and lymphatic system disorders
ANAEMIA	84/198 (42.4%)	95	67/196 (34.2%)	83
LEUKOPENIA	24/198 (12.1%)	42	19/196 (9.7%)	32
NEUTROPENIA	71/198 (35.9%)	122	66/196 (33.7%)	105
THROMBOCYTOPENIA	31/198 (15.7%)	45	29/196 (14.8%)	44
Endocrine disorders
HYPERTHYROIDISM	11/198 (5.6%)	11	5/196 (2.6%)	5
HYPOTHYROIDISM	20/198 (10.1%)	20	1/196 (0.5%)	1
Gastrointestinal disorders
CONSTIPATION	51/198 (25.8%)	61	58/196 (29.6%)	69
DIARRHOEA	32/198 (16.2%)	42	30/196 (15.3%)	46
NAUSEA	74/198 (37.4%)	99	64/196 (32.7%)	89
STOMATITIS	11/198 (5.6%)	11	9/196 (4.6%)	9
VOMITING	38/198 (19.2%)	47	31/196 (15.8%)	45
General disorders
ASTHENIA	23/198 (11.6%)	27	19/196 (9.7%)	25
CHEST PAIN	16/198 (8.1%)	19	12/196 (6.1%)	12
FATIGUE	51/198 (25.8%)	65	49/196 (25%)	61
OEDEMA PERIPHERAL	13/198 (6.6%)	14	7/196 (3.6%)	8
PYREXIA	18/198 (9.1%)	29	16/196 (8.2%)	18
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	14/198 (7.1%)	16	16/196 (8.2%)	19
URINARY TRACT INFECTION	12/198 (6.1%)	16	5/196 (2.6%)	5
Injury, poisoning and procedural complications
INFUSION RELATED REACTION	10/198 (5.1%)	13	8/196 (4.1%)	9
Investigations
NEUTROPHIL COUNT DECREASED	37/198 (18.7%)	74	45/196 (23%)	80
PLATELET COUNT DECREASED	25/198 (12.6%)	36	28/196 (14.3%)	39
WEIGHT DECREASED	20/198 (10.1%)	20	10/196 (5.1%)	11
WHITE BLOOD CELL COUNT DECREASED	18/198 (9.1%)	35	24/196 (12.2%)	43
Metabolism and nutrition disorders
DECREASED APPETITE	54/198 (27.3%)	62	36/196 (18.4%)	39
HYPOKALAEMIA	8/198 (4%)	8	17/196 (8.7%)	18
HYPOMAGNESAEMIA	12/198 (6.1%)	17	9/196 (4.6%)	9
HYPONATRAEMIA	10/198 (5.1%)	10	12/196 (6.1%)	14
Musculoskeletal and connective tissue disorders
ARTHRALGIA	18/198 (9.1%)	20	13/196 (6.6%)	16
BACK PAIN	17/198 (8.6%)	17	19/196 (9.7%)	21
MUSCULOSKELETAL PAIN	12/198 (6.1%)	14	11/196 (5.6%)	13
PAIN IN EXTREMITY	13/198 (6.6%)	13	6/196 (3.1%)	7
Nervous system disorders
DIZZINESS	19/198 (9.6%)	22	11/196 (5.6%)	14
HEADACHE	24/198 (12.1%)	28	23/196 (11.7%)	25
Psychiatric disorders
INSOMNIA	15/198 (7.6%)	18	13/196 (6.6%)	13
Respiratory, thoracic and mediastinal disorders
COUGH	18/198 (9.1%)	22	25/196 (12.8%)	29
DYSPNOEA	19/198 (9.6%)	22	16/196 (8.2%)	17
HAEMOPTYSIS	14/198 (7.1%)	20	10/196 (5.1%)	10
OROPHARYNGEAL PAIN	12/198 (6.1%)	15	5/196 (2.6%)	6
PRODUCTIVE COUGH	10/198 (5.1%)	10	9/196 (4.6%)	14
Skin and subcutaneous tissue disorders
ALOPECIA	73/198 (36.9%)	75	68/196 (34.7%)	71
PRURITUS	12/198 (6.1%)	12	9/196 (4.6%)	10
RASH	14/198 (7.1%)	21	11/196 (5.6%)	13
RASH MACULO-PAPULAR	10/198 (5.1%)	10	2/196 (1%)	3
Vascular disorders
HYPERTENSION	15/198 (7.6%)	20	6/196 (3.1%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.