Clinical Trials Register

Summary
EudraCT Number:	2011-001422-23
Sponsor's Protocol Code Number:	PCD4989g
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-04-02
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

UK - MHRA

A.2

EudraCT number

2011-001422-23

A.3

Full title of the trial

A PHASE I, OPEN LABEL, DOSE ESCALATION STUDY OF THE SAFETY AND PHARMACOKINETICS OF ATEZOLIZUMAB (MPDL3280A) ADMINISTERED INTRAVENOUSLY AS A SINGLE AGENT TO PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS OR HEMATOLOGIC MALIGNANCIES

A.3.1

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

Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) Administered Intravenously As a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors or Hematologic malignancies

A.4.1

Sponsor's protocol code number

PCD4989g

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01375842

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	Genentech Inc
B.1.3.4	Country	United States
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	Genentech, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Quintiles
B.5.2	Functional name of contact point	Carlos Cantú
B.5.3	Address:
B.5.3.1	Street Address	6700 W. 115th Street, Overland Park
B.5.3.2	Town/ city	Kansas
B.5.3.3	Post code	66211
B.5.3.4	Country	United States
B.5.4	Telephone number	+1512-358-0636
B.5.5	Fax number	+1512-410-2971
B.5.6	E-mail	carlos.cantu@quintiles.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	ATEZOLIZUMAB
D.3.4	Pharmaceutical form	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.3.9.3	Other descriptive name	anti-PDL1
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	125
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	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	ATEZOLIZUMAB
D.3.4	Pharmaceutical form	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.3.9.3	Other descriptive name	anti-PDL1
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.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced or Metastatic Solid Tumors or Hematologic Malignancies

E.1.1.1

Medical condition in easily understood language

Advanced or Metastatic Solid Tumors or Hematologic Malignancies

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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10029000
E.1.2	Term	Neoplasm NOS
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 safety and tolerability of atezolizumab administered by intravenous (IV) infusion every 3 weeks (q3w) to patients with locally advanced or metastatic solid tumors or hematologic malignancies
•To determine the maximum tolerated dose (MTD) and to evaluate the dose limiting toxicities (DLTs) of atezolizumab when administered as a single agent to patients by IV infusion q3w
•To identify a recommended Phase II dose of atezolizumab

E.2.2

Secondary objectives of the trial

Pharmacokinetic Objectives:
• To evaluate the pharmacokinetics of atezolizumab when administered as a single agent
• To characterize the immunogenic potential of atezolizumab by measuring anti- atezolizumab antibodies

Activity Objective:
• To make a preliminary assessment of the anti-tumor activity of atezolizumab administered as a single agent

Exploratory Objectives:
• To make a preliminary assessment of biomarkers that might act as pharmacodynamic (PD) indicators of anti-tumor activity of atezolizumab administered as a single agent
• To make a preliminary assessment of biomarkers that might act as predictors of anti-tumor activity of atezolizumab administered as a single agent administered as a single agent

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age ≥ 18 years
• Histologically or cytologically documented, incurable or metastatic solid malignancy that is advanced (non -resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists. Tumor type-specific criteria are detailed in Appendix G.
• Representative tumor specimens in paraffin blocks/unstained slides with an associated pathology report
• Adequate hematologic and end organ function
• Measurable disease per RECIST
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of atezolizumab
• ECOG: 0-1. Patients with ECOG Performance Status of 2, secondary to the underlying disease, may be enrolled after consultation with the Medical Monitor

b. Inclusion Criteria Unique to Patients Undergoing Serial Biopsy in the Serial Biopsy Dose-Expansion Cohort:
• Baseline tumor tissue samples consisting of core needle biopsies for deep tumor tissue or organs or excisional or punch biopsies for cutaneous or subcutaneous lesions will be obtained.

E.4

Principal exclusion criteria

• Known primary central nervous system (CNS) malignancy or untreated or active CNS metastases
• History of autoimmune disease (i.e. SLE, RA, inflammatory bowel disease, autoimmune thyroid disease, vasculitis, etc.)
• History of HIV, hepatitis B, or hepatitis C infection. Patients with past or resolved Hepatitis B are eligible. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA
• Any signs or symptoms of infection
• Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., CLL Rai Stage 0, prostate cancer with Gleason score ≤ 6, and PSA ≤ 10 mg/mL, etc.)

E.5 End points

E.5.1

Primary end point(s)

The safety and tolerability of atezolizumab administered as a single agent therapy for patients with locally advanced or metastatic solid tumors or hematologic malignancies will be assessed using the following primary safety outcome measures:
• Incidence and nature of DLTs
• Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0

E.5.1.1

Timepoint(s) of evaluation of this end point

As defined in the study protocol

E.5.2

Secondary end point(s)

Safety will also be assessed using the following secondary safety endpoints:
• Incidence of anti therapeutic antibody (ATA) response and the potential correlation with PK, PD, and safety parameters
• Changes in vital signs and ECG parameters
• Changes in clinical laboratory results
• Number of cycles and dose intensity
In addition as defined in the study protocol, pharmacokinetic, activity and explanatory outcomes are defined.

E.5.2.1

Timepoint(s) of evaluation of this end point

As defined in the study protocol

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability and biomarkers in tumor samples

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

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)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

France

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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 trial is defined as the completion of the last patient, last visit (LPLV)

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

439

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

216

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

Yes

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

214

F.4.2.2

In the whole clinical trial

689

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)

Atezolizumab treatment will be given as long as the patient continues to experience clinical benefit in the opinion of the investigator until the earlier of unacceptable toxicity, symptomatic deterioration attributed to disease progression, or any of the other reasons for treatment discontinuation as listed in Protocol Section 4.6

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

2012-03-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-09-30

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