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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04338269




Registration number
NCT04338269
Ethics application status
Date submitted
6/04/2020
Date registered
8/04/2020
Date last updated
9/11/2020

Titles & IDs
Public title
A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment
Scientific title
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
Secondary ID [1] 0 0
WO41994
Universal Trial Number (UTN)
Trial acronym
CONTACT-03
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Renal Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Cabozantinib

Experimental: Atezo+Cabo - Participants will receive atezolizumab every 3 weeks on Day 1 of each 21-day cycle (1 cycle=21 days) plus oral tablets of cabozantinib every day.

Active Comparator: Cabozantinib - Participants will receive cabozantinib every day.


Treatment: Drugs: Atezolizumab
Atezolizumab 1200 mg will be administered at a fixed dose on Day 1 of each 21-day cycle by IV infusion every 3 weeks.

Treatment: Drugs: Cabozantinib
Cabozantinib 60 mg (three 20-mg tablets) administered orally once daily.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS), as assessed by Independent Review Facility (IRF) - Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, as assessed by Independent Review Facility (IRF-PFS) or death from any cause, whichever occurs first.
Timepoint [1] 0 0
Randomization up to approximately 27 months
Primary outcome [2] 0 0
Overall survival (OS) - Overall survival (OS), defined as the time from randomization to death from any cause.
Timepoint [2] 0 0
Randomization up to approximately 52 months
Secondary outcome [1] 0 0
PFS Assessed by the Investigators (INV-PFS) - PFS assessed by the investigators (INV-PFS), defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first).
Timepoint [1] 0 0
Randomization up to approximately 27 months
Secondary outcome [2] 0 0
Investigator Assessed Objective Response Rate (INV-ORR) - INV-ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1.
Timepoint [2] 0 0
Randomization up to approximately 27 months
Secondary outcome [3] 0 0
IRF Assessed Objective Response Rate (IRF-ORR) - IRF-ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1.
Timepoint [3] 0 0
Randomization up to approximately 27 months
Secondary outcome [4] 0 0
Investigator Assessed Duration of Objective Response (INV-DOR) - INV-DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) according to RECIST v1.1.
Timepoint [4] 0 0
Randomization up to approximately 27 months
Secondary outcome [5] 0 0
IRF Assessed DOR (IRF-DOR) - IRF-DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) according to RECIST v1.1.
Timepoint [5] 0 0
Randomization up to approximately 27 months
Secondary outcome [6] 0 0
Percentage of Participants With Adverse Events
Timepoint [6] 0 0
Randomization up to approximately 27 months
Secondary outcome [7] 0 0
Atezolizumab Concentrations
Timepoint [7] 0 0
At pre-defined intervals from first administration of study drug up to approximately 27 months
Secondary outcome [8] 0 0
Cabozantinib Concentrations
Timepoint [8] 0 0
At pre-defined intervals from first administration of study drug up to approximately 27 months
Secondary outcome [9] 0 0
Prevalence of Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [9] 0 0
Baseline
Secondary outcome [10] 0 0
Incidence of ADAs to Atezolizumab During the Study
Timepoint [10] 0 0
At pre-defined intervals from first administration of study drug up to approximately 27 months

Eligibility
Key inclusion criteria
- Histologically confirmed locally advanced or metastatic clear cell or non-clear cell
(papillary and unclassified only) RCC. RCC with sarcomatoid features is allowed.

- Radiographic disease progression during or following treatment with ICI for locally
advanced or metastatic RCC either in first- or second-line treatment. ICI is defined
by anti-PD-L1 or anti-PD1 antibody including atezolizumab, avelumab, pembrolizumab, or
nivolumab. Only patients for whom the immediate preceding line of therapy was an ICI
are allowed.

- Measurable disease per RECIST v1.1

- Evaluable IMDC risk score

- Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening,
if clinically feasible

- KPS score of >=70

- Adequate hematologic and end-organ function

- Negative HIV test at screening

- 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

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception and agreement to refrain from donating
eggs

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
a condom, and agreement to refrain from donating sperm
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Treatment with anti-cancer therapy within 28 days prior to initiation of study
treatment

- Patients received cabozantinib at any time prior to screening

- Patients who received more than 1 regimen of ICIs

- Patients who received more than 2 prior lines of therapy in the advanced or metastatic
setting

- Patients who received ICI in the adjuvant setting (adjuvant VEGFR-TKI except
cabozantinib is allowed)

- Patients who have received a mammalian target of rapamycin (mTOR) inhibitor in the
advanced or metastatic setting

- Symptomatic, untreated, or actively progressing CNS metastases

- History of leptomeningeal disease

- Uncontrolled 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,
with the exception of malignancies with a negligible risk of metastasis or death

- 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 final dose of atezolizumab and 4 months after final dose of
cabozantinib

- Severe infection within 4 weeks prior to initiation of study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia

- Uncontrolled hypertension defined as sustained blood pressure >150 mm Hg systolic or >
90 mm Hg diastolic despite optimal antihypertensive treatment

- Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, MI, or cerebrovascular accident) within 3 months prior to
initiation of study treatment, unstable arrhythmia, or unstable angina

- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1

- History of congenital QT syndrome

- History or presence of an abnormal ECG that is clinically significant in the
investigator's opinion

- Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin
inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors
(e.g. clopidogrel)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Orange Hospital - Orange
Recruitment hospital [2] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [3] 0 0
Icon Cancer Foundation - South Brisbane
Recruitment hospital [4] 0 0
Bendigo Cancer Centre - Bendigo
Recruitment hospital [5] 0 0
Box Hill Hospital; Oncology - Box Hill
Recruitment postcode(s) [1] 0 0
2800 - Orange
Recruitment postcode(s) [2] 0 0
2109 - Sydney
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3550 - Bendigo
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
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Colorado
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United States of America
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Connecticut
Country [5] 0 0
United States of America
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District of Columbia
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United States of America
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Florida
Country [7] 0 0
United States of America
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Maryland
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United States of America
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Massachusetts
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Nevada
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United States of America
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New Jersey
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New York
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North Carolina
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Ohio
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Oregon
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United States of America
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Pennsylvania
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Texas
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Utah
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Virginia
Country [19] 0 0
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Wisconsin
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Argentina
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Buenos Aires
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Argentina
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Ciudad Autonoma Bs As
Country [22] 0 0
Argentina
State/province [22] 0 0
Ciudad Autonoma Buenos Aires
Country [23] 0 0
Canada
State/province [23] 0 0
Manitoba
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Denmark
State/province [25] 0 0
Herlev
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Denmark
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Odense C
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France
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Besançon Cedex
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France
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Bordeaux
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France
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Caen
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France
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Clermont Ferrand
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France
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Lille
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France
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Lyon
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France
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Nice
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France
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Nimes
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Paris
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Strasbourg
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Toulouse
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France
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Villejuif
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Chemnitz
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Frankfurt
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Freiburg
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Halle (Saale)
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Hamburg
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Hannover
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Muenster
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Germany
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München
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Germany
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Tübingen
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Ulm
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Greece
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Athens
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Larissa
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Greece
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Lazio
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Lombardia
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Marche
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Piemonte
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Umbria
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Fukuoka
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Gyeongsangnam-do
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Jeollanam-do
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Seongnam-si
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Bytom
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Otwock
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Warszawa
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Wroclaw
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Russian Federation
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Moskovskaja Oblast
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Russian Federation
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Barnaul
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Russian Federation
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Moscow
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Russian Federation
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Novosibirsk
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Spain
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Asturias
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Spain
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Barcelona
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Spain
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Cantabria
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Spain
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Cordoba
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Spain
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Islas Baleares
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Spain
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Madrid
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Spain
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Pontevedra
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Spain
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Burgos
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Spain
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Caceres
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Spain
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Lugo
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Spain
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Malaga
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Spain
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Murcia
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Navarra
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Sevilla
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Spain
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Valencia
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United Kingdom
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Blackburn
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United Kingdom
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Leicester
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London
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United Kingdom
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Manchester
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Exelixis
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Chugai
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase III, multicenter, randomized, open-label study designed to evaluate the
efficacy and safety of atezolizumab given in combination with cabozantinib versus
cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal
cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune
Checkpoint Inhibitor (ICI) treatment in the metastatic setting.
Trial website
https://clinicaltrials.gov/show/NCT04338269
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: WO41994 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04338269