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

2024-517785-42-00 Protocol WO41994 Therapeutic confirmatory (Phase III) Ended

Start 8 Oct 2020 · End 25 Mar 2025 · Status Ended · 2 EU/EEA countries · 8 sites · Protocol WO41994

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 292
Countries 2
Sites 8

Renal cell carcinoma (RCC)

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

Key facts

Sponsor
F. Hoffmann-La Roche AG
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
8 Oct 2020 → 25 Mar 2025
Decision date (initial)
2024-11-01
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
F. Hoffmann-La Roche AG

External identifiers

EU CT number
2024-517785-42-00
EudraCT number
2020-000502-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Others

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

Secondary objectives 4

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

Conditions and MedDRA coding

Renal cell carcinoma (RCC)

VersionLevelCodeTermSystem organ class
21.1 PT 10067946 Renal cell carcinoma 100000004864

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 A study to assess the efficacy and safety of atezolizumab & cabozatinib in patients with RCC
This study will assess the efficacy and safety of atezolizumab when given in combination with cabozantinib compared with cabozantinib alone in patients with advanced clear-cell or non–clear-cell renal cell carcinoma (RCC; papillary, chromophobe or unclassified only) who experienced radiographic tumor progression during or after immune checkpoint inhibitor (ICI) treatment in the adjuvant and/or locally advanced/metastatic setting. With the rapidly evolving landscape of treatments for metastatic RCC, the use of ICI based treatments is moving to earlier lines of therapy and is becoming the standard of care for first- and second-line treatments in most countries. Thus, there remains a need to better understand the sequential use of all available RCC treatments and develop effective treatments that fit this evolving landscape.
 Randomised Controlled None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. 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
  2. Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1
  3. Evaluable International Metastatic Renal Cell Carcinoma Database Consortium risk scores
  4. Radiographic disease progression to prior immune checkpoint inhibitor (ICI) therapy for RCC
  5. Karnofsky Performance Status score of >= 70
  6. Adequate hematologic and end-organ function

Exclusion criteria 6

  1. Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
  2. Patients who received cabozantinib at any time prior to screening
  3. Patients who received more than one ICI treatment in the locally advanced or metastatic setting
  4. Patients who received more than two prior lines of therapy in the locally advanced or metastatic setting
  5. Patients who have received a mammalian target of rapamycin inhibitor in any setting
  6. Symptomatic, untreated, or actively progressing CNS metastases

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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

Secondary endpoints 9

  1. 1. Progression-free survival as assessed by investigators
  2. 2. Investigator- and IRF-assessed objective response rate
  3. 3. Investigator- and IRF-assessed duration of objective response
  4. 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. 5. Change from baseline in targeted vital signs
  6. 6. Change from baseline in targeted clinical laboratory test results
  7. 7. Atezolizumab concentrations at specified timepoints (for atezolizumab + cabozantinib arm)
  8. 8. Cabozantinib concentrations at specified timepoints
  9. 9. Prevalence of anti-drug antibodies (ADAs) to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study (for atezolizumab+ cabozantinib arm)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Tecentriq 1 200 mg concentrate for solution for infusion

PRD5434939 · Product

Active substance
Atezolizumab
Substance synonyms
RO5541267
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
IV INFUSION
Max daily dose
1200 mg milligram(s)
Max total dose
20.40 g gram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01FF05 — -
Marketing authorisation
EU/1/17/1220/001
MA holder
ROCHE REGISTRATION GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Relabeled and repackaged for Clinical trial use

RO7047650

PRD11197468 · Product

Active substance
Cabozantinib
Substance synonyms
XL-184, Cyclopropane-1,1-dicarboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide
Other product name
Cabozantinib
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
60 mg milligram(s)
Max total dose
21.90 g gram(s)
Max treatment duration
12 Month(s)
Authorisation status
Not Authorised
MA holder
EXELIXIS
Paediatric formulation
No
Orphan designation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

213 Total trials 63 Recruiting 141 Ended
Commercial
Sponsor organisation
F. Hoffmann-La Roche AG
Address
Grenzacherstrasse 124
City
Basel
Postcode
4058
Country
Switzerland

Scientific contact point

Organisation
F. Hoffmann-La Roche AG
Contact name
Trial Information System - TISL

Public contact point

Organisation
F. Hoffmann-La Roche AG
Contact name
Trial Information System - TISL

Third parties 7

OrganisationCity, countryDuties
CellCarta
ORG-100039881
 Antwerp, Belgium Laboratory analysis
Labcorp Central Laboratory Services SARL
ORG-100011524
 Meyrin, Switzerland Laboratory analysis
Icon Development Solutions LLC
ORG-100012400
 Whitesboro, United States Laboratory analysis
Median Technologies
ORG-100041462
 Valbonne, France Laboratory analysis
IQVIA Limited
ORG-100008655
 Reading, United Kingdom Other
Alliance Pharma Inc.
ORG-100046000
 Malvern, United States Laboratory analysis
Almac Group Limited
ORG-100011829
 Craigavon, United Kingdom (Northern Ireland) Other, Interactive response technologies (IRT)

Locations

2 EU/EEA countries · 8 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Ended 28 3
Poland Ended 36 5
Rest of world
Japan, United Kingdom, Australia, Argentina, United States, Russian Federation, Korea, Republic of, Canada
 — 228 —

Investigational sites

Germany

3 sites · Ended
Universitaetsklinikum Tuebingen AöR
Klinik für Urologie, Hoppe-Seyler-Strasse 3, Nordstadt, Tuebingen
Universitaetsklinikum Ulm AöR
Klinik für Urologie und Kinderurologie, Albert-Einstein-Allee 23, Eselsberg, Ulm
Klinikum rechts der Isar der TU Muenchen AöR
Urologische Klinik und Poliklinik, Ismaninger Strasse 22, Au-Haidhausen, Munich

Poland

5 sites · Ended
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Ambulatorium Chemioterapii, Ul. Izabeli Romanowskiej 2, 85-796, Bydgoszcz
Europejskie Centrum Zdrowia Otwock Sp. z o.o.
Oddział onkologii klinicznej, Ul. Borowa 14/18, 05-400, Otwock
Uniwersytecki Szpital Kliniczny W Poznaniu
Oddział Chemioterapii, Ul. Augustyna Szamarzewskiego 84, 60-569, Poznan
Dolnoslaskie Centrum Onkologii Pulmonologii I Hematologii
Oddział onkologii klinicznej/chemioterapii, Pl. Ludwika Hirszfelda 12, 53-413, Wroclaw
Szpital Grochowski Im.Dr Med. Rafała Masztaka Sp. z o.o.
Oddział Chemioterapii, Ul. Grenadierow 51/59, 04-073, Warsaw

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Germany 2020-10-20 2024-12-19 2020-10-23 2021-12-27
Poland 2020-10-08 2025-03-24 2020-10-13 2021-12-27

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
WO41994_Summary of Results
SUM-121585
 2026-03-03T10:44:23 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
WO41994_Lay Person Summary Reports 2026-03-03T11:08:41 Submitted Laypersons Summary of Results

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Laypersons summary of results (for publication) lps-2024-517785-42-00_de N/A
Laypersons summary of results (for publication) lps-2024-517785-42-00_engl N/A
Laypersons summary of results (for publication) lps-2024-517785-42-00_pl N/A
Protocol (for publication) d1_protocol-2022-502689-26-00-redacted 6
Recruitment arrangements (for publication) K1 Recruitment Arrangement_Placeholder_WO41994 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF main_REDACTED 8
Subject information and informed consent form (for publication) L1_SIS and ICF MAIN_WO41994 6
Subject information and informed consent form (for publication) L1_SIS and ICF Optional Biopsy 1
Subject information and informed consent form (for publication) L1_SIS and ICF PPA 2
Subject information and informed consent form (for publication) L1_SIS and ICF RBR 2
Subject information and informed consent form (for publication) L1_SIS and ICF RBR_WO41994 2
Subject information and informed consent form (for publication) L1_SIS and ICF to continue after suspected progression 1
Subject information and informed consent form (for publication) L1_SIS and ICF_treatm_after PD_WO41994 1
Summary of results (for publication) CTIS Final Results Submission for WO41994 N/A
Synopsis of the protocol (for publication) d1_protocol-synopsis-2022-502689-26-00 NA

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-26 Germany Acceptable
2024-10-31
 2024-11-01

Related clinical trials