A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment

NCT04338269 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: WO41994
• Study Type: interventional
• Target: 522
• Locations: 15 countries
• Sites: 135

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.

Conditions

Carcinoma, Renal Cell

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1

  PFS was defined as the time from randomization to the first occurrence to PD, as determined by the IRF per RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm). Data for participants who did not experience PD or death was censored at the last tumor assessment date. Data for participants with no post-baseline tumor assessments was censored at the randomization date. PFS was estimated using Kaplan-Meier (KM) method.

  From randomization to the first occurrence of PD according to RECIST v1.1, or death from any cause, whichever occurred first (up to 2 years 5 months)

• Overall Survival (OS)

  OS was defined as the time from randomization to death due to any cause. Data for participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants without post-baseline information were censored at the date of randomization. OS was estimated using KM method.

  From randomization to death due to any cause (up to 2 years 5 months).

Secondary Outcomes (9)

• PFS Assessed by the Investigators (INV-PFS), According to RECIST v1.1

  From randomization to the first occurrence of PD according to RECIST v1.1, or death from any cause, whichever occurred first (up to 2 years 5 months)

• Investigator-assessed Objective Response Rate (ORR) (INV-ORR), According to RECIST v1.1

  Up to 2 years 5 months

• IRF-assessed ORR (IRF-ORR) According to RECIST v1.1

  Up to 2 years 5 months

• Investigator-assessed Duration of Response (DOR) (INV-DOR), According to RECIST v1.1

  From the date of first occurrence of a documented objective response to PD or death from any cause, whichever occurred first (up to 2 years 5 months)

• IRF-assessed DOR (IRF-DOR) According to RECIST v1.1

  From the date of first occurrence of a documented objective response to PD or death from any cause, whichever occurred first (up to 2 years 5 months)

Study Arms (2)

Atezo+Cabo

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Cabozantinib

Cabozantinib

ACTIVE COMPARATOR

Participants will receive cabozantinib every day.

Drug: Cabozantinib

Interventions

Atezolizumab DRUG

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

Also known as: Tecentriq

Atezo+Cabo

Cabozantinib DRUG

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

Also known as: Cabometyx

Atezo+Cabo; Cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed locally advanced or metastatic clear cell or non-clear cell (papillary, chromophobe, and unclassified only) RCC. RCC with sarcomatoid features is allowed. Patients with the chromophobe subtype of non-clear cell RCC must have sarcomatoid differentiation.
• Radiographic disease progression to prior ICI therapy for RCC. Patients who experienced radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. ICI is defined by anti-PD-L1 or anti-PD1 antibody including atezolizumab, avelumab, pembrolizumab, durvalumab, 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. Both archival and fresh samples are preferred.
• KPS score of \>=70
• Recovery to baseline or Grade \</= 1 NCI CTCAE v5.0 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 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

You may not qualify if:

• Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
• Patients 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 (mTOR) inhibitor in any 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, or any active infection that, in the opinion of the investigator, could impact patient safety

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Exelixis: collaborator
• Chugai Pharmaceutical: collaborator

Study Sites (135)

University of Arizona

Tucson, Arizona, 85724-5030, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UC San Diego Health System

La Jolla, California, 92093, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Center - Denver

Littleton, Colorado, 80120, United States

Location

Woodlands Medical Specialists, P.A.

Pensacola, Florida, 32503, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Minnesota Oncology Hematology

Minneapolis, Minnesota, 55404, United States

Location

Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

Las Vegas, Nevada, 89169, United States

Location

Memorial Sloan Kettering - Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

New York Oncology Hematology,P.C.-Albany

Albany, New York, 12208, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Texas Oncology - Central South

Austin, Texas, 78731, United States

Location

University Of Utah

Salt Lake City, Utah, 84108, United States

Location

Virginia Cancer Specialists - Gainsville

Gainesville, Virginia, 20155, United States

Location

Fundación CENIT para la Investigación en Neurociencias

Buenos Aires, C1125ABD, Argentina

Location

Inst. Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

Location

Hospital Britanico

Ciudad Autonoma Bs As, C1280AEB, Argentina

Location

Centro Medico Austral OMI

Ciudad Autonoma Buenos Aires, C1019ABS, Argentina

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

Location

Orange Hospital

Orange, New South Wales, 2800, Australia

Location

Icon Cancer Foundation

South Brisbane, Queensland, 4101, Australia

Location

Bendigo Cancer Centre

Bendigo, Victoria, 3550, Australia

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre

Bordeaux, 33075, France

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital Europeen Georges Pompidou

Paris, 75908, France

Location

ICANS

Strasbourg, 67200, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Zeisigwaldkliniken Bethanien

Chemnitz, 09130, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, 60590, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie

Halle, 06120, Germany

Location

Uniklinik-Eppendorf

Hamburg, 20246, Germany

Location

Med. Hochschule Hannover, Hämatologie, Hämostaseologie, Onkologie u. Stammzelltransplantation

Hanover, 30625, Germany

Location

Klinikum rechts der Isar der TU München

München, 81675, Germany

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Alexandras General Hospital of Athens

Athens, 115 28, Greece

Location

Attikon University General Hospital

Athens, 12464, Greece

Location

Athens Medical Center

Athens, 151 25, Greece

Location

University Hospital of Larissa

Larissa, 41110, Greece

Location

Diavalkaniko Hospital

Thessaloniki, 570 01, Greece

Location

A.O. Universitaria Ospedale Consorziale Policlinico Di Bari

Bari, Apulia, 70124, Italy

Location

Istituto Tumori Napoli

Naples, Campania, 80131, Italy

Location

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

Meldola, Emilia-Romagna, 47014, Italy

Location

Policlinico Universitario "Agostino Gemelli"

Rome, Lazio, 00168, Italy

Location

Asst Degli Spedali Civili Di Brescia

Brescia, Lombardy, 25123, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, 20133, Italy

Location

Fondazione Salvatore Maugeri

Pavia, Lombardy, 27100, Italy

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

Location

Fondazione del Piemonte per l?Oncologia (IRCCS)

Candiolo (TO), Piedmont, 10060, Italy

Location

Ospedale Di Macerata

Macerata, The Marches, 62100, Italy

Location

Azienda Ospedaliera S. Maria - Terni

Terni, Umbria, 05100, Italy

Location

A.O.U di Verona Policlinico G.B. Rossi

Verona, Veneto, 37134, Italy

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

University of Tsukuba Hospital

Ibaraki, 305-8576, Japan

Location

Yokohama City University Hospital

Kanagawa, 236-0004, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Osaka Metropolitan University Hospital

Osaka, 545-8586, Japan

Location

Tokushima University Hospital

Tokushima, 770-8503, Japan

Location

Keio University Hospital

Tokyo, 160-8582, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, 162-8666, Japan

Location

Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna

?ód?, 90-338, Poland

Location

Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny

Brzozów, 36-200, Poland

Location

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

Bydgoszcz, 85-796, Poland

Location

SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4

Bytom, 41-902, Poland

Location

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii

Otwock, 05-400, Poland

Location

Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu

Późna, 60-569, Poland

Location

Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.

Warsaw, 04-073, Poland

Location

Wojskowy Instytut Medyczny

Warsaw, 04-141, Poland

Location

Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii

Wroc?aw, 53-413, Poland

Location

St-Petersburg Regional Oncology Dispensary

Kuzmolovo, Leningrad, 188663, Russia

Location

Branch of the company "Hadassah Medical LTD"

Innovatsionnogo Tsentra Skolkovo, Moscow Oblast, 121205, Russia

Location

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

Moscow, Moscow Oblast, 115478, Russia

Location

MEDSI Clinical Hospital on Pyatnitsky Highway

Moscow, Moscow Oblast, 143422, Russia

Location

SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"

Moskva, Moscow Oblast, 111123, Russia

Location

National Medical Research Center for Surgery named after A.V. Vishnevsky

Moskva, Moscow Oblast, 117997, Russia

Location

Private Healthcare Institution Clinical Hospital RZhD Medicine

Saint Petersburg, Sankt-Peterburg, 195271, Russia

Location

AV Medical Ltd.

Saint Petersburg, Sankt-Peterburg, 199034, Russia

Location

Regional Clinical Oncology Hospital

Yaroslavl, Yaroslavl Oblast, 150054, Russia

Location

Medical Center Avicenna

Novosibirsk, 630099, Russia

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

CHA Bundang Medical Center

Gyeonggi-do, 13496, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Pusan National University Yangsan Hospital

Gyeongsangnam-do, 50612, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Samsung Medical Center

Seoul, 006351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07014, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Hospital de Navarra

Navarra, Navarre, 31008, Spain

Location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, 36213, Spain

Location

Hospital Univ. Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital San Pedro De Alcantara

Cáceres, 10003, Spain

Location

Hospital Lucus Augusti

Lugo, 27003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Virgen de Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario la Fe

Valencia, 46026, Spain

Location

Royal Blackburn Hospital

Blackburn, BB2 3HH, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Barts & London School of Med

London, EC1A 7BE, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Christie Hospital Nhs Trust

Manchester, M2O 4BX, United Kingdom

Location

Related Publications (2)

• Pal SK, Albiges L, Tomczak P, Suarez C, Voss MH, de Velasco G, Chahoud J, Mochalova A, Procopio G, Mahammedi H, Zengerling F, Kim C, Osawa T, Angel M, Gupta S, Khan O, Bergthold G, Liu B, Kalaitzidou M, Huseni M, Scheffold C, Powles T, Choueiri TK. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023 Jul 15;402(10397):185-195. doi: 10.1016/S0140-6736(23)00922-4. Epub 2023 Jun 5.

  PMID: 37290461 DERIVED

• Yang Y, Psutka SP, Parikh AB, Li M, Collier K, Miah A, Mori SV, Hinkley M, Tykodi SS, Hall E, Thompson JA, Yin M. Combining immune checkpoint inhibition plus tyrosine kinase inhibition as first and subsequent treatments for metastatic renal cell carcinoma. Cancer Med. 2022 Aug;11(16):3106-3114. doi: 10.1002/cam4.4679. Epub 2022 Mar 18.

  PMID: 35304832 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

atezolizumab; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 8, 2020
• Study Start: July 28, 2020
• Primary Completion: January 3, 2023
• Study Completion: March 24, 2025
• Last Updated: March 19, 2026
• Results First Posted: February 28, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

GB (5); AU (4); PL (9); RU (10); JP (8); ES (21); DE (10); FR (10); US (24); AR (4); GR (5); KR (9); IT (13); CA (2); DK (1)