Clinical Trials Register

Summary
EudraCT Number:	2014-005490-37
Sponsor's Protocol Code Number:	WO29522
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-03-18
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2014-005490-37

A.3

Full title of the trial

A PHASE III, MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB (ANTI−PD-L1 ANTIBODY) IN COMBINATION WITH NAB-PACLITAXEL COMPARED WITH PLACEBO WITH NAB-PACLITAXEL FOR PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC TRIPLE-NEGATIVE BREAST CANCER

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A trial of MPDL3280A and nab-Paclitaxel in metastatic triple negative breast cancer

A.4.1

Sponsor's protocol code number

WO29522

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	F. Hoffmann La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genentech Inc. c/o F. Hoffmann La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MPDL3280A-RO5541267-F-03
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Atezolizumab
D.3.9.2	Current sponsor code	RO5541267
D.3.9.3	Other descriptive name	MPDL3280A
D.3.9.4	EV Substance Code	SUB126162
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Abraxane
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	nab-paclitaxel
D.3.2	Product code	RO024-7506
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.4	EV Substance Code	SUB09583MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tecentriq
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Atezolizumab
D.3.2	Product code	RO5541267
D.3.4	Pharmaceutical form	Concentrate for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Atezolizumab
D.3.9.2	Current sponsor code	RO5541267
D.3.9.3	Other descriptive name	TECENTRIQ
D.3.9.4	EV Substance Code	SUB190577
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Previously untreated metastatic triple negative breast cancer

E.1.1.1

Medical condition in easily understood language

Metastatic breast cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic breast cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• to evaluate the efficacy of MPDL3280A + nab-paclitaxel compared with placebo + nab-paclitaxel as measured by progression-free survival (PFS; per investigator assessment using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1)
• To evaluate the efficacy of atezolizumab + nab-paclitaxel compared with
placebo + nab-paclitaxel as measured by overall survival (OS)

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of atezolizumab + nab-paclitaxel compared with
placebo + nab-paclitaxel as measured by objective response rate (ORR; per
investigator assessment using RECIST v1.1)
• To evaluate the efficacy of atezolizumab + nab-paclitaxel compared with
placebo + nab-paclitaxel as measured by duration of objective response (DOR; per
investigator using RECIST v1.1) among patients with an objective response
• To evaluate patient-reported outcomes (PROs) of health status/health-related
quality of life (HRQoL) associated with atezolizumab + nab-paclitaxel compared with
placebo + nab-paclitaxel, as measured by the time to deterioration (TTD) in
Items 29 and 30 of the European Organisation for Research and Treatment of
Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Women aged ≥ 18 years
• Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
• No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
• Representative FFPE tumor specimens in paraffin blocks (preferred) or at least
15 unstained slides, with an associated pathology report documenting ER, PR, and HER2 negativity
•A tumor specimen obtained from metastatic or locally advanced disease (if applicable) must be submitted if clinically feasible
• ECOG performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Measurable disease, as defined by RECIST v1.1
•Adequate hematologic and end-organ function defined by laboratory results obtained within 2 weeks prior to first study treatment.
•Women of child bearing potential must agree to use adequate contraception (double barrier
methods of birth control or abstinence) prior to study entry, for the duration of study treatment, and for at least 5 months after the last dose of study treatment.
• Patients who are not postmenopausal (≥ 12 months of non−therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug

E.4

Principal 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 > 2 weeks prior to randomization
• Known CNS disease, except for treated asymptomatic CNS metastases
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites (indwelling drainage catheters are permitted)
• Uncontrolled tumor-related pain
• Uncontrolled hypercalcemia
•Pregnancy or lactation
• Evidence of significant uncontrolled concomitant disease that could affect compliance with
the protocol or interpretation of results, including significant liver disease (such as cirrhosis,
uncontrolled major seizure disorder, or superior vena cava syndrome)
• Significant cardiovascular disease
• Severe infection within 4 weeks prior to randomization, including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• History of autoimmune disease (Autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and Type 1 diabetes mellitus on an stable insulin regimen may be eligible for this study)
• Prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis,
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or
evidence of active pneumonitis on screening chest CT scan.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Positive test for HIV
• Active hepatitis B or hepatitis C
•Active tuberculosis
•Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial.
Low dose steroids for nausea, adrenocortical insufficiency or orthostatic hypotension, IV contrast allergic reactions and inhaled corticosteroids are permitted.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival (PFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Tumor assessments will be performed every 8 weeks for the first 12 months and every 12 weeks thereafter until disease progression or treatment discontinuation, whichever is later

E.5.2

Secondary end point(s)

Overall survival (OS), Objective response rate (ORR) and duration of objective response (DOR), Patient reported outcomes (PRO) of health status and health quality of life (HRQoL)

E.5.2.1

Timepoint(s) of evaluation of this end point

OS - every 3 months until death, withdrawal of consent, loss to follow-up, or study
termination by the Sponsor
ORR and DOR – tumor assessments will be performed every 8 weeks for the first 12 months and every 12 weeks thereafter until disease progression or treatment discontinuation, whichever is later
PRO and HRQoL - at baseline (Cycle 1,Day 1); at Day 1 of each subsequent cycle; and at the treatment discontinuation visit. In
addition, all patients will complete the PRO questionnaires every 28 days for 1 year after
treatment discontinuation, regardless of whether the patient is receiving subsequent
anti-cancer therapy.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Belgium

Canada

Czech Republic

Denmark

Estonia

Finland

France

Germany

Greece

Hungary

Italy

Korea, Republic of

Latvia

Norway

Poland

Portugal

Romania

Slovenia

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is expected to occur about 53 months after FPI when
approximately the pre-planned number of deaths will have been observed

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

540

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

360

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

700

F.4.2.2

In the whole clinical trial

900

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The Sponsor will evaluate the appropriateness of continuing to provide MPDL3280A to
patients assigned to this treatment after evaluating the primary and secondary efficacy
outcome measures and safety data gathered in the study. These analyses may be
conducted prior to completion of the study.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-07-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-08-31

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