Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma

NCT ID: NCT04987203

Last Updated: 2025-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

343 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-09

Study Completion Date

2025-12-30

Brief Summary

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This study will be comparing tivozanib in combination with nivolumab to tivozanib alone in subjects with advanced Renal Cell Carcinoma (RCC) who have had 1 or 2 prior lines of therapy, one of which was an Immune Checkpoint Inhibitor (ICI).

Detailed Description

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This will be an open-label, randomized, controlled, multicenter, multi-national, parallel-arm study. The study is designed to compare the progression free survival (PFS), overall survival (OS), Objective response rate (ORR), duration of response (DoR), and safety of tivozanib and the combination of tivozanib with nivolumab.

Approximately 326 subjects with refractory advanced RCC at approximately 190 sites will be randomized in a 1:1 ratio to treatment with tivozanib plus nivolumab (163 subjects) or tivozanib (163 subjects). Subjects will be randomly assigned to a treatment.

Subjects will receive 1.34 mg/day (monotherapy arm) or 0.89mg/day (combination arm) of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug. One cycle will be defined as 4 weeks: 3 weeks on treatment and 1 week off treatment. Subjects who receive nivolumab will be infused with 1 treatment of nivolumab at specified dose on specified days of each Cycle.

Subjects with documented stable disease or an objective response may continue to receive both tivozanib and nivolumab therapy at the same dose and schedule until progression as long as the tolerability is acceptable. Nivolumab will be discontinued in all subjects after 2 years; Tivozanib may be continued after discontinuation of nivolumab until other withdrawal criteria are met. A Safety Follow-up Visit will be performed 30 days (± 7 days) after the last dose of study drug.

Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tivozanib in Combination with Nivolumab

Subjects with advanced RCC will receive 0.89 mg of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug and nivolumab every 4 weeks on Day 1 of each Cycle, until disease progression or unacceptable toxicities occur, other withdrawal criteria are met, or completion of 2 years of treatment \[for nivolumab\] whichever occurs first.

Group Type EXPERIMENTAL

Tivozanib

Intervention Type DRUG

Tivozanib will be administered orally.

Nivolumab

Intervention Type DRUG

Nivolumab will be administered via intravenous infusion.

Tivozanib

Subjects with advanced RCC will receive 1.34 mg of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug until disease progression or unacceptable toxicities occur, or other withdrawal criteria are met.

Group Type EXPERIMENTAL

Tivozanib

Intervention Type DRUG

Tivozanib will be administered orally.

Interventions

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Tivozanib

Tivozanib will be administered orally.

Intervention Type DRUG

Nivolumab

Nivolumab will be administered via intravenous infusion.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Radiographic disease progression during or following at least 6 weeks of treatment with ICI for locally advanced or metastatic RCC with a clear cell component either in first- or second-line treatment.
* Subjects must have recovered from the adverse events of prior therapy to grade ≤ 1 or baseline.
* Histologically or cytologically confirmed RCC with a clear cell component.
* Measurable disease per RECIST criteria Version 1.1.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* All participants must follow protocol defined contraceptive measures.

Exclusion Criteria

* Subjects who received: a. A single agent tyrosine kinase inhibitor (TKI) in the first line setting followed by a single agent immune checkpoint inhibitor (ICI) in the second line setting; b. More than 2 prior lines of therapy in the advanced or metastatic setting.
* History of life-threatening toxicity related to prior immune therapy.
* Active autoimmune disease as well as those that required discontinuation of prior immuno-oncological (IO) therapy due to immune mediated AEs.
* Uncontrolled hypertension.
* More than 1 prior line of therapy with a checkpoint inhibitor in the metastatic setting.
* Subjects on immune suppressive therapy for organ transplant or subjects with a history of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV) \[Patients with HIV who have CD4+ T-cell counts \>350 cells/µL, without a history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections, and are on established antiretroviral therapy which does not include a cytochrome P450 (CYP)3A4 inducer, for at least 4 weeks and have an HIV viral load less than 400 copies/mL, are eligible\].
* History of clinically significant interstitial lung disease or current non-infectious pneumonitis.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

AVEO Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Chao Family Comprehensive Cancer Center, UC Irvine

Irvine, California, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

Leland Stanford Junior University

Redwood City, California, United States

Site Status

Kaiser Permanente Riverside Medical Center

Riverside, California, United States

Site Status

US Oncology - Rocky Mountain Cancer Centers - Midtown

Denver, Colorado, United States

Site Status

Florida Cancer Specialists & Res Inst

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists & Research Institute (FCS) - Tampa Cancer Center Location

St. Petersburg, Florida, United States

Site Status

The University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

University of Kentucky UK Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Tulane Cancer Center Clinic - Oncology

New Orleans, Louisiana, United States

Site Status

University of Maryland Medical Center-Greenebaum Cancer Ctr

Baltimore, Maryland, United States

Site Status

John Hopkins Medicine - Hematology/oncology

Baltimore, Maryland, United States

Site Status

Maryland Oncology Hematology

Clinton, Maryland, United States

Site Status

Dana-Farber Cancer Institute - Medicine

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

St. Vincent Frontier Cancer Center

Billings, Montana, United States

Site Status

Oncology Hematology West PC dba Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

Memorial Sloan Kettering Cancer Center - Monmouth - Oncology

Middletown, New Jersey, United States

Site Status

University of New Mexico - Comprehensive Cancer Center

Albuquerque, New Mexico, United States

Site Status

Roswell - Roswell Park Cancer Institute - Medical Oncology

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center - Westchester

East White Plains, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center - Nassau

Uniondale, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Lehigh Valley Physician Group

Allentown, Pennsylvania, United States

Site Status

Allegheny General Hospital (AGH)

Pittsburgh, Pennsylvania, United States

Site Status

UH Cleveland Medical Center

Columbia, South Carolina, United States

Site Status

Chattanooga Oncology and Hematology Associates

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Oncology - Central Austin Cancer Center

Austin, Texas, United States

Site Status

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

US Oncology Texas Oncology (CCC of South Texas) - San Antonio Medical Center

San Antonio, Texas, United States

Site Status

University Of Washington - Medical Center

Seattle, Washington, United States

Site Status

Northwest Medical Specialties PLLC

Tacoma, Washington, United States

Site Status

Centro Oncológico Korben

Buenos Aires, Ciudad Autónoma de Buenos Aire, Argentina

Site Status

Clínica Viedma

Viedma, Río Negro Province, Argentina

Site Status

Centro Oncologico de Rosario

Rosario, Santa Fe Province, Argentina

Site Status

Centro para la Atención Integral del paciente Oncológico

San Miguel de Tucumán, Tucumán Province, Argentina

Site Status

Liverpool Hospital Cancer Therapy Centre

Liverpool, New South Wales, Australia

Site Status

Mater Misericordiae Limited

Brisbane, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Sunshine Hospital

Geelong, Victoria, Australia

Site Status

ZNA Jan Palfijn

Merksen, Antwerpen, Belgium

Site Status

Institut Jules Bordet - Oncologie Médicale

Anderlecht, Brussels Capital, Belgium

Site Status

Jessa Ziekenhuis - Campus Virga Jesse - Medische Oncologie

Hasselt, Limburg, Belgium

Site Status

UZ Gent - Medische Oncologie

Ghent, Oost-Vlaanderen, Belgium

Site Status

CHU Brugmann - Victor Horta

Brussels, , Belgium

Site Status

AZ Groeninge - Campus Kennedylaan

Kortrijk, , Belgium

Site Status

Centro Gaucho Integrado de Onc

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, Brazil

Site Status

Universidade Estadual de Campi

Campinas, São Paulo, Brazil

Site Status

Instituto Brasileiro de Controle do Cancer - ibcc

São Paulo, São Paulo, Brazil

Site Status

Hospital Nossa Senhora da Conc

Porto Alegre, , Brazil

Site Status

Pontificia Universidade

Porto Alegre, , Brazil

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

BC Cancer - Vancouver Centre

Vancouver, British Columbia, Canada

Site Status

Sunnybrook Research Institute, sunnybrook Health Sciences Ct

Toronto, Ontario, Canada

Site Status

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

ACEREY Centro de Investigación Clínica Oncológica

Viña del Mar, Región de Valparaíso, Chile

Site Status

Centro de Estudios Clinicos In

Santiago, Región Metropolitana de Santia, Chile

Site Status

Centro de Estudios Clínicos SAGA SpA

Santiago, Región Metropolitana de Santia, Chile

Site Status

Meditek Ltda.

Santiago, Santiago Metropolitan, Chile

Site Status

University Hospital Brno

Brno, Brno-město, Czechia

Site Status

Fakultni Thomayerova nemocnice

Prague, Praha 4, Czechia

Site Status

FN Hradec Kralove

Hradec Králové, , Czechia

Site Status

FN Kralovske Vinohrady

Prague, , Czechia

Site Status

Institut de cancérologie de Strasbourg Europe - ICANS

Strasbourg, Alsace, France

Site Status

Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Site Status

Institut Paoli Calmettes - Hôpital de jour

Marseille, Bouches-du-Rhône, France

Site Status

Hopital Saint-Andre - Service d'Oncologie Medicale

Bordeaux, Gironde, France

Site Status

Hopital Foch

Suresnes, Hauts-de-Seine, France

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CHU Michallon - Hopital Nord - Cancérologie Et Hématologie

Grenoble, Isère, France

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Hôpital privé Le Bois

Lille, Nord, France

Site Status

Centre Hospitalier de Poitiers

Poitiers, Poitou-Charentes, France

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Centre Leon Berard - departement d'oncologie medicale

Lyon, Rhône, France

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Clinique Victor Hugo - Hematologie

Le Mans, Sarthe, France

Site Status

CHD Vendee La Roche sur Yon - Gastro-Entérologie

La Roche-sur-Yon, , France

Site Status

Centre de Lutte Contre le Cancer (CLCC)

Nice, , France

Site Status

ICO - Site Rene Gauducheau - Oncologie Medicale

Saint-Herblain, , France

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Hopital Trousseau - medical oncology

Tours, , France

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Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

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Centre de Lutte Contre le Cancer (CLCC) - Gustave Roussy (Institut de Cancerologie Gustave-Roussy)

Villejuif, Île-de-France Region, France

Site Status

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Site Status

Ospedale S.Donato, AUSL 8 di Arezzo

Arezzo, Arezzo, Italy

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Azienda Mater Domini

Catanzaro, Catanzaro, Italy

Site Status

P.O. Ss. Annunziata

Chieti Scalo, Chieti, Italy

Site Status

IRST

Meldola (Fc), Forli, Italy

Site Status

European Institute of Oncology

Milan, Milano, Italy

Site Status

IRCCS Policlinico San Matteo

Pavia, Pavia, Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Roma, Italy

Site Status

AO S.Camillo-Forlanini

Roma, Roma, Italy

Site Status

Azienda Ospedaliera Santa Maria di Terni

Terni, Terni, Italy

Site Status

PO di Cremona, ASST di Cremona - Oncologia medica

Cremona, , Italy

Site Status

AOUC Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Site Status

IRCCS Fondazione "Giovanni Pas

Napoli, , Italy

Site Status

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Tlalpan, , Mexico

Site Status

Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu

Poznan, Greater Poland Voivodeship, Poland

Site Status

Szpital Specjalistyczny im. L. Rydygiera w Krakowie

Krakow, Lesser Poland Voivodeship, Poland

Site Status

Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina

Otwock, Masovian Voivodeship, Poland

Site Status

Szpital Specjalist. w Brzozowie,Podkarpacki Ośrodek Onkologi

Brzozów, Podkarpackie Voivodeship, Poland

Site Status

Nzoz Mrukmed Lekarz Beata Madej-Mruk I Partner Sp. P.

Rzeszów, Podkarpackie Voivodeship, Poland

Site Status

COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Wojewodzki Szpital Specjalistyczny

Biała Podlaska, , Poland

Site Status

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych

Warsaw, , Poland

Site Status

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, , Poland

Site Status

Hospital Particular do Algarve - Gambelas-Faro

Faro, Faro District, Portugal

Site Status

H. Prof. Doutor Fernando Fonseca

Amadora, Lisbon District, Portugal

Site Status

H. de Santa Maria. Centro Hospitalar Lisboa Norte - Oncologia

Lisbon, Lisbon District, Portugal

Site Status

H. Santo Antonio. Centro Hospitalar do Porto

Porto, Porto District, Portugal

Site Status

Instituto Português Oncologia Francisco Gentil do Porto

Porto, , Portugal

Site Status

H.G.U. de Elche

Elche, Alicante, Spain

Site Status

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Site Status

Hospital de La Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Site Status

Hospital Universitario Vall d'

Barcelona, Barcelona, Spain

Site Status

Institut Catalá d´Oncología (I.C.O.)

Barcelona, Barcelona, Spain

Site Status

Hospital Del Mar

Barcelona, Barcelona, Spain

Site Status

Hospital Universitari Parc Tau

Sabadell, Barcelona, Spain

Site Status

ICO-Hospital Universitari de G

Girona, Girona, Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Site Status

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Site Status

Hospital U. 12 Octubre

Madrid, Madrid, Spain

Site Status

Hospital Universitario La Paz

Madrid, Madrid, Spain

Site Status

Hospital Universitario Virgen

Seville, Sevilla, Spain

Site Status

Fundación Instituto Valenciano

Valencia, Valencia, Spain

Site Status

Hospital Universitario Y Politécnico La Fe

Valencia, Valenciana, Comunidad, Spain

Site Status

C.H.U. de Orense

Ourense, , Spain

Site Status

Addenbrooke's Hospital - Oncology

Cambridge, Cambridgeshire, United Kingdom

Site Status

Mount Vernon Cancer Centre

Northwood, England, United Kingdom

Site Status

Royal Blackburn Hospital - Oncology

Preston, Lancashire, United Kingdom

Site Status

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, London, City of, United Kingdom

Site Status

The Christie NHS Foundation Trust - Medical Oncology

Manchester, Manchester, United Kingdom

Site Status

Royal Marsden - Sutton

Sutton, Surrey, United Kingdom

Site Status

Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Site Status

New Cross Hospital

Wolverhampton, Wolverhampton, United Kingdom

Site Status

Royal Derby Hospital

Derby, , United Kingdom

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Brazil Canada Chile Czechia France Germany Italy Mexico Poland Portugal Spain United Kingdom

References

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Choueiri TK, Albiges L, Barthelemy P, Iacovelli R, Emambux S, Molina-Cerrillo J, Garmezy B, Barata P, Basu A, Bourlon MT, Moon H, Ratta R, McKay RR, Chehrazi-Raffle A, Hammers H, Heng DYC, Braendle E, Beckermann KE, McGregor BA, Motzer RJ. Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study. Lancet. 2024 Oct 5;404(10460):1309-1320. doi: 10.1016/S0140-6736(24)01758-6. Epub 2024 Sep 13.

Reference Type DERIVED
PMID: 39284329 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35304832 (View on PubMed)

Other Identifiers

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AV-951-20-304

Identifier Type: -

Identifier Source: org_study_id

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