IMpassion131: A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03125902
• Collaborator: (none)
• Enrollment: 651
• Locations: 161
• Arms: 2
• Anticipated Duration (Months): 58.2
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Phase 3, multicenter, randomized, double-blind, placebo controlled study is designed to evaluate the efficacy and safety of atezolizumab (MPDL3280A, an anti-programmed death-ligand 1 [PD-L1] antibody) administered in combination with paclitaxel compared with placebo in combination with paclitaxel in participants with previously untreated, inoperable locally advanced or metastatic, centrally confirmed TNBC. Participants will be randomized in a 2:1 ratio to receive atezolizumab or placebo plus paclitaxel until disease progression or unacceptable toxicity or end of study, whichever occurs first (maximum up to approximately 40 months). In addition, the Sponsor may decide to terminate the study at any time.

Condition or Disease	Intervention/Treatment	Phase
Triple-Negative Breast Cancer	Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody; Drug: Atezolizumab Placebo; Drug: Paclitaxel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 651 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: The Sponsor and its agents; the study site personnel, including the investigator; and the participant will be blinded to treatment assignment.
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomised, Double-Blind, Placebo-Controlled Study of Atezolizumab (Anti-Pd-L1 Antibody) in Combination With Paclitaxel Compared With Placebo With Paclitaxel for Patients With Previously Untreated Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer
• Actual Study Start Date: Aug 25, 2017
• Actual Primary Completion Date: Nov 15, 2019
• Anticipated Study Completion Date: Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo and Paclitaxel Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody; Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.; Other Names: MPDL3280A, TECENTRIQ ; Drug: Paclitaxel; Paclitaxel will be administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.
Experimental: Atezolizumab and Paclitaxel Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Drug: Atezolizumab Placebo; Placebo matching to atezolizumab will be administered via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.; Drug: Paclitaxel; Paclitaxel will be administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Subpopulation With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [From Day 1 to disease progression (PD) or death from any cause, assessed up to primary completion date (approximately 26 months)]

   PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

2. Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population [From Day 1 to disease progression (PD) or death from any cause, assessed up to primary completion date (approximately 26 months)]

   PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

Secondary Outcome Measures

1. Overall Survival (OS) in the PD-L1-Positive Subpopulation [From Day 1 to death from any cause, assessed up to primary completion date (approximately 26 months)]

   OS is defined as the time from randomization to death from any cause. Results from a pre-specified interim analysis.

2. Overall Survival (OS) in the ITT Population [From Day 1 to death from any cause, assessed up to primary completion date (approximately 26 months)]

   OS is defined as the time from randomization to death from any cause. Results from a pre-specified interim analysis.

3. Percentage of Participants Who Are Alive at 12 and 18 Months [From Day 1 to death from any cause, assessed up to 12 and 18 months]

   Results from a pre-specified interim analysis.

4. Time to Deterioration (TTD) in Global Health Status/ Health Related Quality of Life (HRQoL) in the PRO Evaluable Population [From Day 1 to deterioration, assessed up to primary completion date (approximately 26 months)]

   Deterioration in Global Health Status/HRQoL is defined as a decrease of at least 10 points on the Global Health Status /HRQoL scale (comprised of 2 items: 29 and 30) of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The 2 items use 7-point scale (1 = very poor to 7 = Excellent). Scores are averaged, transformed to 0-100 scale; where higher score=better level of functioning or greater degree of symptoms.

5. Percentage of Participants Who Are Alive Without Progression Event at Month 12 Assessed Using RECIST v1.1 [From Day 1 to PD or death from any cause, assessed up to 12 months]

   PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

6. Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Confirmed, Investigator-Assessed ) [From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

   Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.

7. Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Unconfirmed, Investigator-Assessed) [From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

   Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD.

8. Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Confirmed, Investigator-Assessed ) [From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

   Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.

9. Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Unconfirmed, Investigator-Assessed ) [From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

   Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD.

10. Duration of Objective Response (DOR) Assessed Using RECIST v1.1 in DOR-evaluable Population (Unconfirmed) [From objective response to PD, assessed up to primary completion date (approximately 26 months)]

    DOR is defined as the time period from the date of initial CR or PR until the date of PD or death from any cause, whichever occurs first. CR is defined as the disappearance of all TLs and SA reduction to <10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

11. Percentage of Participants With Clinical Benefit Assessed Using RECIST v1.1 in Response-evaluable Population [From Day 1 to PD, assessed up to primary completion date (approximately 26 months)]

    Clinical benefit is defined as the achievement of CR, PR, or stable disease according to RECIST v1.1 that lasts for at least 6 months. CR is defined as the disappearance of all TLs and SA reduction to <10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference smallest SD since treatment started.

12. Minimum Observed Serum Concentration (Cmin) of Atezolizumab in PK Evaluable Population [Pre-dose (0 hours) on Day 1 of Cycles 2-4 and at treatment discontinuation (TD), (approximately 9 months).]

13. Maximum Observed Serum Concentration (Cmax) of Atezolizumab in PK-evaluable Population [C1D1 30 min postdose]

14. Minimum Observed Plasma Concentration (Cmin) of Paclitaxel [Pre-dose (0 hours) on Day 1 of Cycle 3 (1 Cycle = 28 days)]

15. Maximum Observed Plasma Concentration (Cmax) of Paclitaxel [Pre-dose (0 hours), 5-10 min before and after paclitaxel infusion, 60 min after paclitaxel infusion on Day 1 of Cycles 1 and 3 (paclitaxel infusion duration= 60 min) (1 Cycle = 28 days)]

16. Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [From Day 1 to 90 days after last dose of study drug, assessed up to primary completion date (approximately 26 months)]

    Investigator text for AEs is coded using MedDRA version 23.0

17. Percentage of Participants With Anti-Drug Antibodies' (ADAs) Against Atezolizumab in ADA Evaluable Population [Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16, and at every 8 cycles thereafter until TD, at TD, and at 90-150 days after TD (maximum up to 45 months) (1 Cycle = 28 days)]

18. Overall Survival by PD-L1 Status, Intent to Treat Population [From Day 1 up to primary completion date (approximately 26 months)]

    Results from a pre-specified interim analysis.

19. Progression Free Survival by PD-L1 Status, Intent to Treat Population [From Day 1 up to primary completion date (approximately 26 months)]

20. Duration of Confirmed Response (C-DoR) in (C-DoR)-Evaluable Population [From objective response to PD, assessed up to primary completion date (approximately 26 months)]

    C-DoR is defined as the time from the first occurrence of a documented confirmed response (CR or PR) in C-DOR evaluable population until the date of disease progression per RECIST v1.1 or death from any cause, whichever occurs first. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants with locally advanced or metastatic, histologically documented TNBC (absence of human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PR] expression), not amenable to surgical therapy

• Participants eligible for taxane monotherapy

• No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC

• Availability of formalin-fixed paraffin-embedded (FFPE) tumor block (preferred) or at least 17 unstained slides, collected ≤3 months prior to randomization, with an associated pathology report, if available. If a tumour sample taken within 3 months before randomisation is not available and a tumour biopsy is not clinically feasible, the primary surgical resection sample or the most recent FFPE tumour biopsy sample may be used. Of these additional options, the most recent sample should be used.

• Eastern Cooperative Oncology Group performance status of 0 or 1

• Life expectancy at least 12 weeks

• Measurable disease, as defined by RECIST v1.1

• Adequate hematologic and end-organ function

• Negative human immunodeficiency virus (HIV) test at screening.

• Negative hepatitis B surface antigen (HBsAg) test at screening

• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive HBcAb test.

• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.

• Women of child bearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug

• For men and women of child bearing potential: agreement to remain abstinent or use protocol defined contraceptive measures during the treatment period and for at least 5 months after the last dose of atezolizumab/placebo, or for at least 6 months after the last dose of paclitaxel

Exclusion Criteria:

• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to randomization

• Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases

• Leptomeningeal disease

• Uncontrolled pleural effusion, pericardial effusion, or ascites

• Uncontrolled tumor-related pain, or uncontrolled hypercalcemia or clinically significant (symptomatic) hypercalcemia

• Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)

• Pregnant or breast-feeding women, or intending to become pregnant during the study

• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease, cardiovascular disease, and presence of an abnormal electrocardiogram (ECG)

• Serious infection requiring antibiotics within 2 weeks prior to randomization, including but not limited to infections requiring hospitalization or IV antibiotics, such as bacteremia, or severe pneumonia

• Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the study other than for diagnosis

• Treatment with investigational therapy within 30 days prior to initiation of study treatment

• History of hypersensitivity reactions to study drug or any component of the study drug formulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center	Stanford	California	United States	94305-5820
2	Florida Cancer Specialists; Department of Oncology	Fort Myers	Florida	United States	33901-8101
3	Florida Cancer Specialist, North Region	Saint Petersburg	Florida	United States	33705
4	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia	United States	30060
5	HCA Midwest Health	Kansas City	Missouri	United States	64132
6	The Valley Hospital	Paramus	New Jersey	United States	07652
7	Magee-Woman's Hospital	Pittsburgh	Pennsylvania	United States	15213
8	Tennessee Oncology; Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
9	Centro Oncologico Riojano Integral (CORI)	La Rioja		Argentina	F5300COE
10	Santa Casa de Misericordia de Salvador	Salvador	BA	Brazil	40050-410
11	Centro de Pesquisas Clinicas em Oncologia - CPCO	Cachoeiro de Itapemirim	ES	Brazil	29308-014
12	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO	Brazil	74605-070
13	Hospital Sao Lucas - PUCRS	Porto Alegre	RS	Brazil	90610-000
14	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS	Brazil	91350-200
15	Hospital Perola Byington	Sao Paulo	SP	Brazil	01317-000
16	Tom Baker Cancer Centre-Calgary	Calgary	Alberta	Canada	T2N 4N2
17	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
18	Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7
19	Grand River Hospital	Kitchener	Ontario	Canada	N2G 1G3
20	London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
21	Sunnybrook Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
22	McGill University; Glen Site; Oncology	Montreal	Quebec	Canada	H4A 3J1
23	Hopital du Saint Sacrement	Quebec City	Quebec	Canada	G1S 4L8
24	Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont	Sherbrooke	Quebec	Canada	J1H 5N4
25	Cancer Hospital Chinese Academy of Medical Sciences.	Beijing		China	100021
26	Beijing Union Hospital	Beijing		China	100730
27	West China Hospital, Sichuan University; Department of Breast	Chengdu		China	610041
28	Sun Yat-sen Memorial Hospital	Guangzhou		China	510000
29	Harbin Medical University Cancer Hospital	Harbin		China	150081
30	Shandong Cancer Hospital	Jinan		China	250117
31	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City		China	210029
32	Jiangsu Cancer Hospital	Nanjing City		China	211100
33	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
34	Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)	Shanghai		China	200025
35	Liaoning cancer Hospital & Institute	Shenyang		China	110042
36	Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)	Shijiazhuang		China	050035
37	Tianjin Medical University Cancer Institute & Hospital	Tianjing		China	300060
38	The Second Affiliated Hospital of Xi'an Jiao Tong University	Xi'an City		China	710004
39	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an		China	710061
40	Zhejiang Cancer Hospital	Zhejiang		China	310022
41	Henan Cancer Hospital	Zhengzhou		China	450008
42	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
43	Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology	Hradec Kralove		Czechia	500 05
44	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc		Czechia	779 00
45	Fakultni nemocnice Ostrava; Klinika onkologicka FNO a LF OU	Ostrava-Poruba		Czechia	70852
46	Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika	Praha 2		Czechia	128 08
47	Clinique Sainte Catherine; Hopital De Semaine	Avignon		France	84918
48	HOPITAL JEAN MINJOZ; Oncologie	Besancon		France	25030
49	Polyclinique Bordeaux Nord Aquitaine	Bordeaux		France	33300
50	Hopital Morvan	Brest		France	29200
51	CHD Les Oudairies	La Roche Sur Yon		France	85925
52	Centre Oscar Lambret; Senologie	Lille		France	59020
53	Centre Leon Berard; Departement Oncologie Medicale	Lyon		France	69373
54	Centre D'Oncologie de Gentilly; Oncology	Nancy		France	54100
55	Hopital Caremeau; Hematologie Oncologie	Nimes		France	30029
56	Hopital Tenon	Paris		France	75020
57	Institut Curie; Oncologie Medicale	Paris		France	75231
58	Hopital Saint Louis, Service D Oncologie Medicale	Paris		France	75475
59	Ch Pitie Salpetriere; Oncologie Medicale	Paris		France	75651
60	Centre Eugene Marquis; Service d'oncologie	Rennes		France	35042
61	Centre Paul Strauss; Oncologie Medicale	Strasbourg		France	67065
62	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse		France	31059
63	Institut Gustave Roussy; Sitep	VILLEJUIF Cedex		France	94805
64	Ambulantes Tumorzentrum Spandau; Dres. Benno Mohr und Uwe Peters	Berlin		Germany	13581
65	Onkologische Schwerpunktpraxis Bielefeld	Bielefeld		Germany	33604
66	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen		Germany	45136
67	HOPA im Struensee-Haus, Dres. Erik Engel, Wiebke Hollburg	Hamburg		Germany	22767
68	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg		Germany	69120
69	St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe	Koeln		Germany	50935
70	Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde	Mainz		Germany	55131
71	OnkoNet Marburg GmbH	Marburg		Germany	35037
72	Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt	München		Germany	80337
73	Gemeinschaftspraxis für Hämatologie und Onkologie	Münster		Germany	48153
74	Klinikum Ernst von Bergmann; Frauenklinik	Potsdam		Germany	14467
75	Dres. Helmut Forstbauer, Carsten Ziske und Kollegen; Onkologische Schwerpunktpraxis	Troisdorf		Germany	53840
76	Universitätsklinik Tübingen; Frauenklinik	Tübingen		Germany	72076
77	Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine	Athens		Greece	115 22
78	ARETAIEION UNIVERSITY HOSPITAL; oncology unit	Athens		Greece	115 28
79	Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.	Kifisia		Greece	145 64
80	Papageorgiou General Hospital; Medical Oncology	Thessaloniki		Greece	564 29
81	Yashoda Hospital	Hyderabad	Andhra Pradesh	India	500082
82	Indraprastha Apollo Hospitals	New Delhi	Delhi	India	110076
83	Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology	New Delhi	Delhi	India	110085
84	Max Super Speciality Hospital; Medical Oncology	North WEST Delhi	Delhi	India	110088
85	Manipal Hospital; Department of Oncology	Bangalore	Karnataka	India	560017
86	Tata Memorial Hospital; Dept of Medical Oncology	Mumbai	Maharashtra	India	400012
87	Jehangir Hospital	Pune	Maharashtra	India	411001
88	TATA Medical Centre; Medical Oncology	Kolkata	WEST Bengal	India	700156
89	Apollo Speciality Hospital	Chennai		India	600035
90	MAX Balaji Hospital	Delhi		India	110092
91	Apollo Gleneagles Hospitals	Kolkata		India	700054
92	Dr. B L Kapur Memorial Hospital; BLK Cancer Centre	New Delhi		India	110005
93	Hadassah Ein Karem Hospital; Oncology Dept	Jerusalem		Israel	9112000
94	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva		Israel	4941492
95	Sheba Medical Center	Ramat Gan		Israel	5262100
96	Rambam Health Corporation; Oncology Institute	Rambam		Israel	3525408
97	Kaplan Medical Center	Rehovot		Israel	7610001
98	Tel Aviv Sourasky Medical Ctr; Oncology	Tel Aviv		Israel	6423906
99	Assaf Harofeh; Oncology	Zerifin		Israel	6093000
100	Fondazione Università G. D'Annunzio; Clinical Research Center (CRC); Centro Studi (CESI)	Chieti	Abruzzo	Italy	66103
101	Presidio Ospedaliero S. Giovanni Di Dio; U.O. Di Oncologia	Frattamaggiore	Campania	Italy	80027
102	Azienda Ospedaliera Universitaria Federico II	Napoli	Campania	Italy	80131
103	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania	Italy	80131
104	Azienda Ospedaliero - Universitaria di Modena Policlinico	Modena	Emilia-Romagna	Italy	41110
105	Universita Campus Bio-Medico di Roma (UCBM)	Roma	Lazio	Italy	00128
106	IRCCS Istituto Regina Elena (IFO); Oncologia Medica B	Roma	Lazio	Italy	00144
107	Azienda Policlinico Umberto I	Roma	Lazio	Italy	00161
108	A.O. Universitaria S. Martino Di Genova	Genova	Liguria	Italy	16132
109	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo	Lombardia	Italy	24127
110	Asst Degli Spedali Civili Di Brescia	Brescia	Lombardia	Italy	25123
111	Hospital San Raffaele	Milano	Lombardia	Italy	20132
112	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia	Italy	20133
113	IEO Istituto Europeo di Oncologia;Divisione Oncologia Medica	Milano	Lombardia	Italy	20141
114	IRCCS Istituto Clinico Humanitas; Oncologia	Rozzano	Lombardia	Italy	20089
115	Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo	Candiolo	Piemonte	Italy	10060
116	Ospedale S. Vincenzo; Oncologia Medica	Taormina	Sicilia	Italy	98030
117	Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia	Firenze	Toscana	Italy	50134
118	Ospedale Civile; Unita Operativa Di Oncologia Medica	Livorno	Toscana	Italy	57100
119	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto	Italy	35128
120	Gunma Prefectural Cancer Center	Gunma		Japan	373-8550
121	Hiroshima City Hiroshima Citizens Hospital	Hiroshima		Japan	730-8518
122	Sagara Hospital	Kagoshima		Japan	892-0833
123	Kanagawa Cancer Center	Kanagawa		Japan	241-8515
124	Tokai University Hospital	Kanagawa		Japan	259-1193
125	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
126	Naha-nishi Clinic	Okinawa		Japan	901-0154
127	Osaka International Cancer Institute	Osaka		Japan	541-8567
128	Saitama Cancer Center	Saitama		Japan	362-0806
129	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
130	Centre Hospitalier Universitaire Mohamed VI; Oncologie-Hématologie	Marrakech		Morocco	40000
131	Institut National D'oncologie Sidi Mohammed Ben Abdellah; Anatomopathologie	Rabat		Morocco	10000
132	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca		Romania	400015
133	Centrul de Oncologie Sfantul Nectarie	Craiova		Romania	200347
134	Petrov Research Inst. of Oncology	Pesochny	Leningrad	Russian Federation	197758
135	Russian Oncology Research Center n.a. N.N. Blokhin	Moscow		Russian Federation	115478
136	King Fahad Specialist Hospital; Oncology	Dammam		Saudi Arabia	31444
137	International Medical Center (IMC)	Jeddah		Saudi Arabia	21451
138	King Fahad Medical City; Gastroentrology	Riyadh		Saudi Arabia	11525
139	Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A	Bratislava		Slovakia	833 10
140	POKO Poprad; Department of Oncology	Poprad		Slovakia	058 01
141	Wilgers Oncology Centre	Pretoria		South Africa	0001
142	Private Oncology Centre	Pretoria		South Africa	0081
143	Sandton Oncology Medical Group	Sandton		South Africa	2196
144	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña	Spain	15006
145	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona		Spain	08036
146	Hospital Universitario de Fuenlabrada; Servicio de Oncologia	Madrid		Spain	28943
147	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla		Spain	41009
148	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
149	Adana Baskent University Medical Faculty; Oncology	Adana		Turkey	01220
150	Ankara City Hospital	Ankara		Turkey	06490
151	Uludag University Medical Faculty; Internal Medicine	Bursa		Turkey	16059
152	Dicle Uni Medical Faculty; Internal Medicine	Diyarbakir		Turkey	10000
153	Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi	Edirne		Turkey	22030
154	Izmir Ataturk Training and Research Hospital	Izmir		Turkey	35965
155	Kocaeli University Faculty of Medicine; Medical oncology	Izmit		Turkey	31380
156	Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology	Kadiköy		Turkey	34722
157	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London		United Kingdom	SE1 9RT
158	Christie Hospital	Manchester		United Kingdom	M20 3BG
159	Mount Vernon Cancer Centre	Northwood		United Kingdom	HA6 2RN
160	K hospital	Hanoi		Vietnam	100000
161	Hochiminh city oncology hospital	Hochiminh city		Vietnam	700000

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Feb 11, 2020
• Statistical Analysis Plan - Mar 25, 2020

More Information

Additional Information:

• Additional information for the IMpassion131
• general information on clinical trials

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03125902
• Other Study ID Numbers: MO39196; 2016-004024-29
• First Posted: Apr 24, 2017
• Last Update Posted: May 16, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Paclitaxel; Atezolizumab; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	The target population included subjects with previously untreated inoperable locally advanced or metastatic TNBC.

Arm/Group Title	Placebo + Paclitaxel	Atezolizumab + Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	220	431
COMPLETED	0	0
NOT COMPLETED	220	431

Baseline Characteristics

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel	Total
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	220	431	651
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	176 80%	322 74.7%	498 76.5%
>=65 years	44 20%	109 25.3%	153 23.5%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.7 (12.2)	54.8 (12.6)	54.0 (12.5)
Sex: Female, Male (Count of Participants)
Female	220 100%	430 99.8%	650 99.8%
Male	0 0%	1 0.2%	1 0.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 10.5%	44 10.2%	67 10.3%
Not Hispanic or Latino	174 79.1%	332 77%	506 77.7%
Unknown or Not Reported	23 10.5%	55 12.8%	78 12%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	66 30%	123 28.5%	189 29%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.2%	1 0.2%
Black or African American	10 4.5%	21 4.9%	31 4.8%
White	128 58.2%	246 57.1%	374 57.5%
More than one race	2 0.9%	3 0.7%	5 0.8%
Unknown or Not Reported	14 6.4%	37 8.6%	51 7.8%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Subpopulation With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status
Description	PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
Time Frame	From Day 1 to disease progression (PD) or death from any cause, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

PD-L1-positive subpopulation: participants in the ITT population whose PD-L1 status was IC1/2/3 at the time of randomization

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	101	191
Median (95% Confidence Interval) [Months]	5.72	5.95

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments	Stratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2032
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2601
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population
Description	PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
Time Frame	From Day 1 to disease progression (PD) or death from any cause, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants, whether or not the assigned study treatment was received

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	220	431
Median (95% Confidence Interval) [Months]	5.55	5.68

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis
Statistical Test of Hypothesis	p-Value	0.1343
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1285
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Survival (OS) in the PD-L1-Positive Subpopulation
Description	OS is defined as the time from randomization to death from any cause. Results from a pre-specified interim analysis.
Time Frame	From Day 1 to death from any cause, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

PD-L1-positive subpopulation: participants in the ITT population whose PD-L1 status was IC1/2/3 at the time of randomization

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	101	191
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments	Stratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1420
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 0.86 to 2.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1374
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 0.86 to 2.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Overall Survival (OS) in the ITT Population
Description	OS is defined as the time from randomization to death from any cause. Results from a pre-specified interim analysis.
Time Frame	From Day 1 to death from any cause, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants, whether or not the assigned study treatment was received

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	220	431
Median (95% Confidence Interval) [Months]	22.80	18.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel
	Comments	Stratified analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.1411
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1097
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Who Are Alive at 12 and 18 Months
Description	Results from a pre-specified interim analysis.
Time Frame	From Day 1 to death from any cause, assessed up to 12 and 18 months

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants, whether or not the assigned study treatment was received

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	220	431
12 months	74.86 34%	68.32 15.9%
18 months	60.95 27.7%	51.02 11.8%

6. Secondary Outcome

Title	Time to Deterioration (TTD) in Global Health Status/ Health Related Quality of Life (HRQoL) in the PRO Evaluable Population
Description	Deterioration in Global Health Status/HRQoL is defined as a decrease of at least 10 points on the Global Health Status /HRQoL scale (comprised of 2 items: 29 and 30) of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The 2 items use 7-point scale (1 = very poor to 7 = Excellent). Scores are averaged, transformed to 0-100 scale; where higher score=better level of functioning or greater degree of symptoms.
Time Frame	From Day 1 to deterioration, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

PRO-evaluable populations: participants in the ITT population with baseline PRO assessment and at least one post-baseline PRO assessment in the questionnaire of interest (European Organization for the Research and Treatment of Cancer [EORTC] Quality-of-life Questionnaire [QLQ] C30, EORTC QLQ BR-23 or FACT-G)

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	205	383
Median (95% Confidence Interval) [Months]	17.35	12.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments	Stratified analysis
Statistical Test of Hypothesis	p-Value	0.8435
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants Who Are Alive Without Progression Event at Month 12 Assessed Using RECIST v1.1
Description	PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
Time Frame	From Day 1 to PD or death from any cause, assessed up to 12 months

Outcome Measure Data

Analysis Population Description

Response-evaluable population: participants in the ITT population with measurable disease at baseline.

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	219	431
Number (95% Confidence Interval) [Percentage of Participants]	16.22 7.4%	21.63 5%

8. Secondary Outcome

Title	Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Confirmed, Investigator-Assessed )
Description	Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.
Time Frame	From Day 1 to PD, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

PD-L1-positive subpopulation: participants in the ITT population whose PD-L1 status was IC1/2/3 at the time of randomization

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	101	191
Number (95% Confidence Interval) [Percentage of Participants]	40.6 18.5%	49.2 11.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1526
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 0.87 to 2.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Unconfirmed, Investigator-Assessed)
Description	Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD.
Time Frame	From Day 1 to PD, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

PD-L1-positive subpopulation: participants in the ITT population whose PD-L1 status was IC1/2/3 at the time of randomization

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	101	191
Number (95% Confidence Interval) [Percentage of Participants]	55.4 25.2%	63.4 14.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1834
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 0.85 to 2.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Confirmed, Investigator-Assessed )
Description	Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.
Time Frame	From Day 1 to PD, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

Response-evaluable population: participants in the ITT population with measurable disease at baseline

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	219	431
Number (95% Confidence Interval) [Percentage of Participants]	32.4 14.7%	39.9 9.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0513
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95%; 1.00 to 2.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Unconfirmed, Investigator-Assessed )
Description	Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD.
Time Frame	From Day 1 to PD, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

Response-evaluable population: participants in the ITT population with measurable disease at baseline

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	219	431
Number (95% Confidence Interval) [Percentage of Participants]	47.5 21.6%	53.6 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1226
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Duration of Objective Response (DOR) Assessed Using RECIST v1.1 in DOR-evaluable Population (Unconfirmed)
Description	DOR is defined as the time period from the date of initial CR or PR until the date of PD or death from any cause, whichever occurs first. CR is defined as the disappearance of all TLs and SA reduction to <10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
Time Frame	From objective response to PD, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

Duration of response (DoR)-evaluable population: participants in the ITT population with measurable disease at baseline

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	104	231
Median (95% Confidence Interval) [Months]	5.45	6.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments	Unstratified Analysis
Statistical Test of Hypothesis	p-Value	0.0641
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit Assessed Using RECIST v1.1 in Response-evaluable Population
Description	Clinical benefit is defined as the achievement of CR, PR, or stable disease according to RECIST v1.1 that lasts for at least 6 months. CR is defined as the disappearance of all TLs and SA reduction to <10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference smallest SD since treatment started.
Time Frame	From Day 1 to PD, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

Clinical Benefit Rate analysis included all participants with unconfirmed PR/CR or SD of at least 6 months duration

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	219	431
Number (95% Confidence Interval) [Percentage of Participants]	49.8 22.6%	57.1 13.2%

14. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Atezolizumab in PK Evaluable Population
Time Frame	Pre-dose (0 hours) on Day 1 of Cycles 2-4 and at treatment discontinuation (TD), (approximately 9 months).

Outcome Measure Data

Analysis Population Description

PK-evaluable population: all participants who received any dose of Atezolizumab and who have at least one evaluable post-baseline PK sample. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Arm/Group Title	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	342
C2D1 predose	139 (53.3)
C3D1 predose	208 (78.3)
C4D1 predose	242 (84.8)

15. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Atezolizumab in PK-evaluable Population
Time Frame	C1D1 30 min postdose

Outcome Measure Data

Analysis Population Description

PK-evaluable population: all participants who received any dose of Atezolizumab and who have at least one evaluable post-baseline PK sample. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Arm/Group Title	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	342
Mean (Standard Deviation) [μg/mL]	321 (90.5)

16. Secondary Outcome

Title	Minimum Observed Plasma Concentration (Cmin) of Paclitaxel
Time Frame	Pre-dose (0 hours) on Day 1 of Cycle 3 (1 Cycle = 28 days)

Outcome Measure Data

Analysis Population Description

PK-evaluable population: first 60 participants who received any dose of Paclitaxel and who have at least one evaluable post-baseline PK sample. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	23	37
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1.51 (NA)	1.67 (NA)

17. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Paclitaxel
Time Frame	Pre-dose (0 hours), 5-10 min before and after paclitaxel infusion, 60 min after paclitaxel infusion on Day 1 of Cycles 1 and 3 (paclitaxel infusion duration= 60 min) (1 Cycle = 28 days)

Outcome Measure Data

Analysis Population Description

PK-evaluable population: first 60 participants who received any dose of Paclitaxel and who have at least one evaluable post-baseline PK sample. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	23	37
C1D1 Post-Dose	518 (290.7)	301 (1501)
C3D1 Post-Dose	666 (339)	276 (1360)

18. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Description	Investigator text for AEs is coded using MedDRA version 23.0
Time Frame	From Day 1 to 90 days after last dose of study drug, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

Safety-evaluable population: participants who received any amount of any study drug. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	218	431
Percentage of participants with at least one AE	97.7 44.4%	99.1 23%
Percentage of participants with at least one SAE	16.1 7.3%	22.7 5.3%

19. Secondary Outcome

Title	Percentage of Participants With Anti-Drug Antibodies' (ADAs) Against Atezolizumab in ADA Evaluable Population
Time Frame	Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16, and at every 8 cycles thereafter until TD, at TD, and at 90-150 days after TD (maximum up to 45 months) (1 Cycle = 28 days)

Outcome Measure Data

Analysis Population Description

Anti-Drug Antibody (ADA) population: Baseline ADA-evaluable population: all participants with at least one evaluable ADA assay result from a baseline sample Post baseline ADA-Evaluable population: all participants with at least one evaluable ADA assay result from at least one post-baseline sample. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Arm/Group Title	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	334
Percentage of participants positive for ADA at Baseline	1.5 0.7%
Percentage of participants positive for ADA Post-baseline	14.7 6.7%

20. Secondary Outcome

Title	Overall Survival by PD-L1 Status, Intent to Treat Population
Description	Results from a pre-specified interim analysis.
Time Frame	From Day 1 up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants, whether or not the assigned study treatment was received

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	220	431
PD-L1 IC0	20.37	16.26
PD-L1 IC1/2/3	NA	NA

21. Secondary Outcome

Title	Progression Free Survival by PD-L1 Status, Intent to Treat Population
Time Frame	From Day 1 up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants, whether or not the assigned study treatment was received

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	220	431
PD-L1 IC0	5.49	5.45
PD-L1 IC1/2/3	5.72	5.95

22. Secondary Outcome

Title	Duration of Confirmed Response (C-DoR) in (C-DoR)-Evaluable Population
Description	C-DoR is defined as the time from the first occurrence of a documented confirmed response (CR or PR) in C-DOR evaluable population until the date of disease progression per RECIST v1.1 or death from any cause, whichever occurs first. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.
Time Frame	From objective response to PD, assessed up to primary completion date (approximately 26 months)

Outcome Measure Data

Analysis Population Description

Duration of confirmed response (C-DoR)-evaluable population: participants in the ITT population with measurable disease at baseline and with a confirmed objective response

Arm/Group Title	Placebo and Paclitaxel	Atezolizumab and Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.	Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Measure Participants	71	172
Median (95% Confidence Interval) [Months]	5.75	7.66

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo and Paclitaxel, Atezolizumab and Paclitaxel
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01227
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.42 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From baseline up to 2 years 3 months (Cutoff Date: 15-Nov-2019)
Adverse Event Reporting Description	All cause mortality table is presented for ITT population and includes deaths due to AEs, unrelated, and those outside of the 90-day reporting period. Serious adverse events and other (non-serious) adverse events are presented for safety population.
Arm/Group Title	Placebo + Paclitaxel		Atezolizumab + Paclitaxel
Arm/Group Description	Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.		Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
All Cause Mortality
	Placebo + Paclitaxel		Atezolizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/218 (24.3%)		126/431 (29.2%)
Serious Adverse Events
	Placebo + Paclitaxel		Atezolizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/218 (16.1%)		98/431 (22.7%)
Blood and lymphatic system disorders
ANAEMIA	2/218 (0.9%)	2	2/431 (0.5%)	2
BICYTOPENIA	0/218 (0%)	0	1/431 (0.2%)	1
BONE MARROW FAILURE	1/218 (0.5%)	1	2/431 (0.5%)	2
FEBRILE NEUTROPENIA	1/218 (0.5%)	1	3/431 (0.7%)	3
LYMPHADENITIS	1/218 (0.5%)	1	0/431 (0%)	0
NEUTROPENIA	0/218 (0%)	0	2/431 (0.5%)	2
THROMBOCYTOPENIA	0/218 (0%)	0	1/431 (0.2%)	1
Cardiac disorders
CARDIAC FAILURE	1/218 (0.5%)	1	1/431 (0.2%)	1
PERICARDITIS	1/218 (0.5%)	1	0/431 (0%)	0
Ear and labyrinth disorders
VERTIGO	0/218 (0%)	0	1/431 (0.2%)	1
Endocrine disorders
HYPOPHYSITIS	1/218 (0.5%)	1	0/431 (0%)	0
HYPOTHYROIDISM	0/218 (0%)	0	1/431 (0.2%)	1
Eye disorders
KERATITIS	0/218 (0%)	0	1/431 (0.2%)	1
ORBITAL MYOSITIS	0/218 (0%)	0	1/431 (0.2%)	1
Gastrointestinal disorders
ABDOMINAL DISTENSION	0/218 (0%)	0	1/431 (0.2%)	1
ABDOMINAL PAIN UPPER	1/218 (0.5%)	1	0/431 (0%)	0
COLITIS	0/218 (0%)	0	1/431 (0.2%)	1
COLITIS ULCERATIVE	0/218 (0%)	0	1/431 (0.2%)	1
DIARRHOEA	1/218 (0.5%)	1	2/431 (0.5%)	2
GASTRIC ULCER	0/218 (0%)	0	1/431 (0.2%)	1
GASTROINTESTINAL ULCER	0/218 (0%)	0	1/431 (0.2%)	1
HAEMATEMESIS	0/218 (0%)	0	1/431 (0.2%)	1
IMMUNE-MEDIATED PANCREATITIS	0/218 (0%)	0	1/431 (0.2%)	1
NAUSEA	0/218 (0%)	0	2/431 (0.5%)	2
PANCREATITIS	0/218 (0%)	0	2/431 (0.5%)	3
PANCREATITIS ACUTE	0/218 (0%)	0	1/431 (0.2%)	1
RECTAL HAEMORRHAGE	1/218 (0.5%)	1	0/431 (0%)	0
VOMITING	3/218 (1.4%)	3	3/431 (0.7%)	3
General disorders
DEATH	0/218 (0%)	0	3/431 (0.7%)	3
INFLUENZA LIKE ILLNESS	0/218 (0%)	0	1/431 (0.2%)	1
MULTIPLE ORGAN DYSFUNCTION SYNDROME	0/218 (0%)	0	1/431 (0.2%)	1
PYREXIA	1/218 (0.5%)	1	3/431 (0.7%)	3
Hepatobiliary disorders
CHOLELITHIASIS	0/218 (0%)	0	1/431 (0.2%)	1
HEPATIC FUNCTION ABNORMAL	1/218 (0.5%)	1	0/431 (0%)	0
HEPATITIS	0/218 (0%)	0	1/431 (0.2%)	1
Immune system disorders
ANAPHYLACTIC REACTION	0/218 (0%)	0	1/431 (0.2%)	1
DRUG HYPERSENSITIVITY	0/218 (0%)	0	1/431 (0.2%)	1
Infections and infestations
BRONCHITIS	0/218 (0%)	0	1/431 (0.2%)	1
DEVICE RELATED INFECTION	0/218 (0%)	0	1/431 (0.2%)	1
DIARRHOEA INFECTIOUS	0/218 (0%)	0	1/431 (0.2%)	1
DIVERTICULITIS	0/218 (0%)	0	1/431 (0.2%)	1
ERYSIPELAS	0/218 (0%)	0	1/431 (0.2%)	1
GASTROENTERITIS	0/218 (0%)	0	1/431 (0.2%)	1
HERPES ZOSTER	1/218 (0.5%)	1	0/431 (0%)	0
INFECTION	2/218 (0.9%)	2	0/431 (0%)	0
INFLUENZA	0/218 (0%)	0	1/431 (0.2%)	1
LOWER RESPIRATORY TRACT INFECTION	0/218 (0%)	0	1/431 (0.2%)	1
MYELITIS	0/218 (0%)	0	1/431 (0.2%)	1
PNEUMOCYSTIS JIROVECII PNEUMONIA	0/218 (0%)	0	1/431 (0.2%)	1
PNEUMONIA	3/218 (1.4%)	3	9/431 (2.1%)	9
POSTOPERATIVE WOUND INFECTION	0/218 (0%)	0	1/431 (0.2%)	1
PULMONARY SEPSIS	0/218 (0%)	0	1/431 (0.2%)	1
PYELONEPHRITIS	0/218 (0%)	0	1/431 (0.2%)	1
SEPSIS	1/218 (0.5%)	1	4/431 (0.9%)	4
SOFT TISSUE INFECTION	1/218 (0.5%)	1	0/431 (0%)	0
STAPHYLOCOCCAL INFECTION	0/218 (0%)	0	1/431 (0.2%)	1
STAPHYLOCOCCAL SKIN INFECTION	0/218 (0%)	0	1/431 (0.2%)	1
TOOTH INFECTION	0/218 (0%)	0	1/431 (0.2%)	1
UPPER RESPIRATORY TRACT INFECTION	1/218 (0.5%)	1	1/431 (0.2%)	1
URINARY TRACT INFECTION	1/218 (0.5%)	1	3/431 (0.7%)	3
UROSEPSIS	1/218 (0.5%)	1	0/431 (0%)	0
VASCULAR DEVICE INFECTION	3/218 (1.4%)	3	2/431 (0.5%)	2
VESTIBULAR NEURONITIS	0/218 (0%)	0	1/431 (0.2%)	1
WOUND INFECTION	0/218 (0%)	0	1/431 (0.2%)	1
Injury, poisoning and procedural complications
COMPRESSION FRACTURE	0/218 (0%)	0	1/431 (0.2%)	1
FEMUR FRACTURE	0/218 (0%)	0	2/431 (0.5%)	2
INFUSION RELATED REACTION	2/218 (0.9%)	2	3/431 (0.7%)	4
PROCEDURAL PNEUMOTHORAX	0/218 (0%)	0	1/431 (0.2%)	1
SPINAL COMPRESSION FRACTURE	0/218 (0%)	0	1/431 (0.2%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/218 (0.5%)	1	2/431 (0.5%)	2
TRANSAMINASES INCREASED	1/218 (0.5%)	1	0/431 (0%)	0
Metabolism and nutrition disorders
DECREASED APPETITE	1/218 (0.5%)	1	0/431 (0%)	0
DIABETES MELLITUS	1/218 (0.5%)	1	1/431 (0.2%)	1
HYPERAMYLASAEMIA	0/218 (0%)	0	1/431 (0.2%)	1
HYPERLIPASAEMIA	0/218 (0%)	0	1/431 (0.2%)	1
HYPOCALCAEMIA	1/218 (0.5%)	1	1/431 (0.2%)	1
HYPONATRAEMIA	0/218 (0%)	0	1/431 (0.2%)	1
HYPOPROTEINAEMIA	1/218 (0.5%)	2	0/431 (0%)	0
Musculoskeletal and connective tissue disorders
BACK PAIN	0/218 (0%)	0	1/431 (0.2%)	1
MUSCULAR WEAKNESS	0/218 (0%)	0	1/431 (0.2%)	1
PAIN IN EXTREMITY	0/218 (0%)	0	2/431 (0.5%)	2
PATHOLOGICAL FRACTURE	0/218 (0%)	0	1/431 (0.2%)	1
POLYMYOSITIS	0/218 (0%)	0	1/431 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO CENTRAL NERVOUS SYSTEM	0/218 (0%)	0	1/431 (0.2%)	1
TUMOUR PAIN	0/218 (0%)	0	1/431 (0.2%)	1
Nervous system disorders
CEREBRAL VENOUS SINUS THROMBOSIS	0/218 (0%)	0	1/431 (0.2%)	1
COGNITIVE DISORDER	0/218 (0%)	0	1/431 (0.2%)	1
DIZZINESS	1/218 (0.5%)	1	0/431 (0%)	0
EPILEPSY	1/218 (0.5%)	1	0/431 (0%)	0
HEADACHE	1/218 (0.5%)	1	0/431 (0%)	0
MYASTHENIA GRAVIS	0/218 (0%)	0	1/431 (0.2%)	1
SCIATICA	1/218 (0.5%)	1	0/431 (0%)	0
SEIZURE	0/218 (0%)	0	1/431 (0.2%)	1
Product Issues
DEVICE BREAKAGE	0/218 (0%)	0	1/431 (0.2%)	1
DEVICE KINK	0/218 (0%)	0	1/431 (0.2%)	1
Psychiatric disorders
DEPRESSION	1/218 (0.5%)	1	0/431 (0%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY	0/218 (0%)	0	2/431 (0.5%)	2
GLOMERULONEPHRITIS CHRONIC	0/218 (0%)	0	1/431 (0.2%)	1
NEPHRITIS	0/218 (0%)	0	1/431 (0.2%)	1
RENAL IMPAIRMENT	0/218 (0%)	0	1/431 (0.2%)	1
Reproductive system and breast disorders
BREAST FIBROSIS	1/218 (0.5%)	1	0/431 (0%)	0
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0/218 (0%)	0	1/431 (0.2%)	1
DYSPNOEA	0/218 (0%)	0	1/431 (0.2%)	1
EPISTAXIS	1/218 (0.5%)	1	0/431 (0%)	0
HAEMOPTYSIS	0/218 (0%)	0	1/431 (0.2%)	1
INTERSTITIAL LUNG DISEASE	0/218 (0%)	0	1/431 (0.2%)	1
LUNG DISORDER	0/218 (0%)	0	1/431 (0.2%)	1
PLEURAL EFFUSION	0/218 (0%)	0	2/431 (0.5%)	2
PNEUMONITIS	0/218 (0%)	0	6/431 (1.4%)	7
PULMONARY EMBOLISM	0/218 (0%)	0	2/431 (0.5%)	2
RESPIRATORY DISTRESS	0/218 (0%)	0	2/431 (0.5%)	2
Vascular disorders
DEEP VEIN THROMBOSIS	0/218 (0%)	0	1/431 (0.2%)	1
HAEMATOMA	1/218 (0.5%)	1	1/431 (0.2%)	1
HYPERTENSIVE CRISIS	1/218 (0.5%)	1	0/431 (0%)	0
HYPOTENSION	1/218 (0.5%)	1	0/431 (0%)	0
THROMBOSIS	0/218 (0%)	0	1/431 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Placebo + Paclitaxel		Atezolizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	209/218 (95.9%)		418/431 (97%)
Blood and lymphatic system disorders
ANAEMIA	60/218 (27.5%)	102	118/431 (27.4%)	229
LEUKOPENIA	15/218 (6.9%)	32	49/431 (11.4%)	148
NEUTROPENIA	46/218 (21.1%)	98	91/431 (21.1%)	215
Endocrine disorders
HYPERTHYROIDISM	0/218 (0%)	0	22/431 (5.1%)	25
HYPOTHYROIDISM	5/218 (2.3%)	5	43/431 (10%)	49
Gastrointestinal disorders
ABDOMINAL PAIN	18/218 (8.3%)	20	34/431 (7.9%)	39
ABDOMINAL PAIN UPPER	14/218 (6.4%)	20	38/431 (8.8%)	43
CONSTIPATION	31/218 (14.2%)	51	79/431 (18.3%)	95
DIARRHOEA	48/218 (22%)	75	117/431 (27.1%)	184
DRY MOUTH	7/218 (3.2%)	8	22/431 (5.1%)	30
DYSPEPSIA	11/218 (5%)	12	16/431 (3.7%)	17
NAUSEA	53/218 (24.3%)	92	111/431 (25.8%)	155
STOMATITIS	10/218 (4.6%)	14	23/431 (5.3%)	27
VOMITING	20/218 (9.2%)	34	66/431 (15.3%)	102
General disorders
ASTHENIA	45/218 (20.6%)	59	99/431 (23%)	139
FATIGUE	55/218 (25.2%)	68	117/431 (27.1%)	148
OEDEMA PERIPHERAL	20/218 (9.2%)	27	42/431 (9.7%)	55
PYREXIA	25/218 (11.5%)	33	62/431 (14.4%)	83
Infections and infestations
NASOPHARYNGITIS	16/218 (7.3%)	17	32/431 (7.4%)	35
UPPER RESPIRATORY TRACT INFECTION	12/218 (5.5%)	14	24/431 (5.6%)	33
URINARY TRACT INFECTION	10/218 (4.6%)	12	32/431 (7.4%)	41
Investigations
ALANINE AMINOTRANSFERASE INCREASED	34/218 (15.6%)	53	79/431 (18.3%)	138
ASPARTATE AMINOTRANSFERASE INCREASED	38/218 (17.4%)	60	80/431 (18.6%)	134
NEUTROPHIL COUNT DECREASED	33/218 (15.1%)	169	62/431 (14.4%)	226
WEIGHT DECREASED	6/218 (2.8%)	6	27/431 (6.3%)	28
WHITE BLOOD CELL COUNT DECREASED	29/218 (13.3%)	165	60/431 (13.9%)	190
Metabolism and nutrition disorders
DECREASED APPETITE	18/218 (8.3%)	27	63/431 (14.6%)	100
Musculoskeletal and connective tissue disorders
ARTHRALGIA	14/218 (6.4%)	18	50/431 (11.6%)	74
BACK PAIN	18/218 (8.3%)	21	38/431 (8.8%)	42
MUSCULOSKELETAL PAIN	9/218 (4.1%)	9	24/431 (5.6%)	25
MYALGIA	23/218 (10.6%)	32	45/431 (10.4%)	56
PAIN IN EXTREMITY	22/218 (10.1%)	33	45/431 (10.4%)	55
Nervous system disorders
DIZZINESS	18/218 (8.3%)	21	32/431 (7.4%)	36
DYSGEUSIA	16/218 (7.3%)	18	32/431 (7.4%)	34
HEADACHE	36/218 (16.5%)	41	51/431 (11.8%)	64
HYPOAESTHESIA	14/218 (6.4%)	18	23/431 (5.3%)	33
NEUROPATHY PERIPHERAL	58/218 (26.6%)	80	117/431 (27.1%)	154
PARAESTHESIA	22/218 (10.1%)	30	37/431 (8.6%)	46
PERIPHERAL SENSORY NEUROPATHY	23/218 (10.6%)	26	41/431 (9.5%)	49
Psychiatric disorders
INSOMNIA	21/218 (9.6%)	21	30/431 (7%)	36
Reproductive system and breast disorders
BREAST PAIN	8/218 (3.7%)	8	26/431 (6%)	31
Respiratory, thoracic and mediastinal disorders
COUGH	35/218 (16.1%)	43	82/431 (19%)	102
DYSPNOEA	24/218 (11%)	29	46/431 (10.7%)	54
EPISTAXIS	15/218 (6.9%)	18	25/431 (5.8%)	29
Skin and subcutaneous tissue disorders
ALOPECIA	116/218 (53.2%)	121	252/431 (58.5%)	256
ERYTHEMA	6/218 (2.8%)	6	24/431 (5.6%)	28
PRURITUS	18/218 (8.3%)	20	40/431 (9.3%)	64
RASH	35/218 (16.1%)	51	73/431 (16.9%)	98
Vascular disorders
HOT FLUSH	11/218 (5%)	12	17/431 (3.9%)	19
HYPERTENSION	11/218 (5%)	11	18/431 (4.2%)	32

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.