Clinical Trials Register

Summary
EudraCT Number:	2020-000502-29
Sponsor's Protocol Code Number:	WO41994
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-08-05
Trial 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

2020-000502-29

A.3

Full title of the trial

A PHASE III, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ATEZOLIZUMAB GIVEN IN COMBINATION WITH CABOZANTINIB VERSUS CABOZANTINIB ALONE IN PATIENTS WITH INOPERABLE, LOCALLY ADVANCED, OR METASTATIC RENAL CELL CARCINOMA WHO EXPERIENCED RADIOGRAPHIC TUMOR PROGRESSION DURING OR AFTER IMMUNE CHECKPOINT INHIBITOR TREATMENT

A.3.1

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

A Study to Evaluate the Efficacy and Safety of Atezolizumab Given in Combination with Cabozantinib Versus Cabozantinib Alone in Patients with Inoperable, Locally Advanced, or Metastatic Renal Cell Carcinoma who Experienced Radiographic Tumor Progression During or After Immune Checkpoint Inhibitor Treatment

A.4.1

Sponsor's protocol code number

WO41994

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. Hoffman-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. Hoffman-La Roche Ltd.
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Exelisis, 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	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	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.3.9.4	EV Substance Code	SUB178312
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	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	Cabozantinib
D.3.2	Product code	RO7047650
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Caboznatinib
D.3.9.2	Current sponsor code	RO7047650
D.3.9.3	Other descriptive name	Cabozantinib S-malate
D.3.9.4	EV Substance Code	SUB176318
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	20
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.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

Renal cell carcinoma (RCC)

E.1.1.1

Medical condition in easily understood language

RCC is the most common type of kidney cancer in adults (responsible for approximately 90-95% of cases)

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10038395
E.1.2	Term	Renal carcinoma
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10038400
E.1.2	Term	Renal carcinoma stage IV
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10050076
E.1.2	Term	Metastatic renal carcinoma
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 atezolizumab in combination with cabozantinib (i.e. atezolizumab + cabozantinib arm) compared with cabozantinib alone (cabozantinib arm) in the intent-to-treat population

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of atezolizumab in combination with cabozantinib compared with cabozantinib alone in the intent-to-treat population
• To evaluate the safety of atezolizumab in combination with cabozantinib compared with cabozantinib alone in the intent-to-treat population
• To characterize the pharmacokinetics profile of atezolizumab and cabozantinib administered in combination
• To evaluate the immune response to atezolizumab (for atezolizumab+ cabozantinib arm)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age >= 18 years
• Histologically confirmed locally advanced or metastatic clear cell or
non-clear cell RCC (papillary, chromophobe and unclassified only). RCC
with sarcomatoid features is allowed. Patients with the chromophobe
subtype of non-clear cell RCC must have sarcomatoid differentiation
• Radiographic disease progression during or following treatment with
immune checkpoint inhibitors (ICI) for locally advanced or metastatic
RCC either in first- or second-line treatment. Patients who experienced
radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. Patients must have received at
least 2 cycles of ICI treatment . ICI must have been used in the
immediate preceding line of therapy. ICI is defined by antiPD-L1 or
antiPD1 antibody including atezolizumab, avelumab, pembrolizumab,
durvalumab or nivolumab. Ipilimumab monotherapy is not considered
an antiPD L1 or antiPD1 therapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors
version 1.1
• Evaluable International Metastatic Renal Cell Carcinoma Database
Consortium risk scores
• Representative pretreatment tumor specimen for exploratory
biomarker research: archival tumor specimen, and pretreatment tumor
tissue from fresh biopsy at screening, if clinically feasible. Both archival
and fresh samples are preferred.
• Karnofsky Performance Status score of >= 70
• Recovery to baseline or Grade <=1 National Cancer Institute Common
Terminology Criteria for Adverse Events Version 5.0 from toxicities
related to any prior treatments, unless adverse events are clinically
nonsignificant and/or stable in the opinion of the investigator. Grade 2
alopecia is allowed for study participation
• Adequate hematologic and end-organ function
• Negative hepatitis B testing at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive
HCV antibody test followed by a negative HCV RNA test at screening
• Negative HIV test at screening
• For women of childbearing potential: agreement to remain abstinent
or use contraception and agree to refrain from donating eggs for 4
months after the final dose of cabozantinib and for 5 months after the
final dose of atezolizumab
• For men: agreement to remain abstinent or use a condom, and
agreement to refrain from donating sperm for 4 months after the final
dose of cabozantinib to avoid exposing the embryo

E.4

Principal exclusion criteria

• Treatment with anti-cancer therapy within 14 days prior to initiation of
study treatment
• Patients who received cabozantinib at any time prior to screening
• Patients who received more than one ICI treatment in the locally
advanced or metastatic setting
• Patients who received more than two prior lines of therapy in the
locally advanced or metastatic setting
• Patients who have received a mammalian target of rapamycin inhibitor
in any setting
• Symptomatic, untreated, or actively progressing CNS metastases
• History of leptomeningeal disease
• Uncontrolled tumor-related pain or pleural effusion, pericardial
effusion, or ascites requiring recurrent drainage procedures,
uncontrolled or symptomatic hypercalcemia or symptomatic
hypercalcemia requiring continued use of bisphosphonate therapy or
denosumab
• History of malignancy other than renal carcinoma within 5 years prior
to screening
• Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1
• Active tuberculosis
• Major surgical procedure, other than for diagnosis, within 4 weeks
prior to initiation of study treatment, or anticipation of need for a major
surgical procedure during the study
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab
and 4 months after the final dose of cabozantinib
• Severe infection within 4 weeks prior to initiation of study
treatment,but not limited to, hospitalization for complications of
infection, bacteremia, or severe pneumonia or any active infection that,
in the opinion of the investigator, could impact patient safety
• Treatment with systemic immunostimulatory agents within 4 weeks or
5 drug-elimination half-lives prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2
weeks prior to initiation of study treatment, or anticipation of need for
systemic immunosuppressive medication during study treatment
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior
to initiation of study treatment
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, metabolic dysfunction, physical examination
finding, or clinical laboratory finding that contraindicates the use of an
investigational drug, may affect the interpretation of the results, or may
render the patient at high risk from treatment complications
• Current treatment with anti-viral therapy for HBV or HCV
• Active or history of autoimmune disease or immune deficiency
• Pharmacologically uncompensated, symptomatic hypothyroidism
• Malabsorption syndrome
• Uncontrolled hypertension
• Tumors invading the GI-tract, active peptic ulcer disease, acute
pancreatitis, acute obstruction of the pancreatic or biliary duct,
appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet
obstruction, or inflammatory bowel disease
• Stroke, myocardial infarction, or other symptomatic ischemic event, or
thromboembolic event within 6 months before first dose randomization
• Significant cardiovascular disease within 3 months prior to initiation of
study treatment
• History of clinically significant ventricular dysrhythmias or risk factors
for ventricular dysrhythmias or congenital QT syndrome
• History or presence of an abnormal ECG that is clinically significant
• Concomitant anticoagulation with coumarin agents, direct thrombin
inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet
inhibitors

E.5 End points

E.5.1

Primary end point(s)

1. Progression-free survival as assessed by Independent Review Facility (IRF)
2. Overall survival

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Approximately 55 months

E.5.2

Secondary end point(s)

1. Progression-free survival as assessed by investigators
2. Investigator- and IRF-assessed objective response rate
3. Investigator- and IRF-assessed duration of objective response
4. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0
5. Change from baseline in targeted vital signs
6. Change from baseline in targeted clinical laboratory test results
7. Atezolizumab concentrations at specified timepoints (for atezolizumab+ cabozantinib arm)
8. Cabozantinib concentrations at specified timepoints
9. Prevalence of anti-drug antibodies (ADAs) to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study (for atezolizumab+ cabozantinib arm)

E.5.2.1

Timepoint(s) of evaluation of this end point

1-4. Approximately 55 months
5-6. From baseline (Day-28 to -1) to 55 months
7. Day 1 of Cycle 1-4, 8, 12, 16 and at treatment discontinuation visit (for atezolizumab+ cabozantinib arm)
8. Day 1 of Cycle 2-4, and at treatment discontinuation visit
9. Day 1 of Cycle 1-4, 8, 12, 16 and at treatment discontinuation visit (for atezolizumab+ cabozantinib arm)

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

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

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)

Yes

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

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

Argentina

Australia

Canada

Japan

Korea, Republic of

United States

Russian Federation

Denmark

France

Germany

Greece

Italy

Poland

Spain

United Kingdom

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 this study is defined as the date when the required numbers of events for the final analysis of OS in the ITT population has occurred.
In addition, the Sponsor may decide to terminate the study at any time.

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:

275

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

225

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

257

F.4.2.2

In the whole clinical trial

500

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 offer continued access to study treatment (atezolizumab and cabozantinib) free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product.

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

2020-08-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-17

P. End of Trial
P.	End of Trial Status	Ongoing

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