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

NCT04987203 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: AV-951-20-304
• Study Type: interventional
• Target: 343
• Locations: 16 countries
• Sites: 139

Brief Summary

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).

Conditions

Renal Cell Carcinoma

Keywords

Immune Checkpoint Inhibitor; Open-label; Monotherapy; Disease Progression

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Comparison of the PFS of tivozanib in combination with nivolumab to tivozanib in subjects with RCC who have progressed following 1 or 2 lines of therapy. PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease \[PD\], radiological) according to Response Evaluation Criteria In Solid Tumors (RECIST), or death due to any reasons whichever comes first.

  Until progressive disease [PD] (Approximately 30 months)

Secondary Outcomes (5)

• Overall Survival

  From Screening (Days -28 to -1) until death (Approximately 42 months)

• Progression free survival

  Until progressive disease [PD] (Approximately 30 months)

• Objective Response Rate

  From Screening (Days -28 to -1) until PD (Approximately 30 months)

• Duration of Response

  From Screening (Days -28 to -1) until PD or death (Approximately 30 months)

• Number of subjects with serious and non-serious adverse events

  From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)

Study Arms (2)

Tivozanib in Combination with Nivolumab

EXPERIMENTAL

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.

Drug: Tivozanib; Drug: Nivolumab

Tivozanib

EXPERIMENTAL

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.

Drug: Tivozanib

Interventions

Tivozanib DRUG

Tivozanib will be administered orally.

Tivozanib; Tivozanib in Combination with Nivolumab

Nivolumab DRUG

Nivolumab will be administered via intravenous infusion.

Tivozanib in Combination with Nivolumab

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead
• Parexel: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (139)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Chao Family Comprehensive Cancer Center, UC Irvine

Irvine, California, 92868, United States

Location

University of California San Diego

La Jolla, California, 92037, United States

Location

Leland Stanford Junior University

Redwood City, California, 94063, United States

Location

Kaiser Permanente Riverside Medical Center

Riverside, California, 92505, United States

Location

US Oncology - Rocky Mountain Cancer Centers - Midtown

Denver, Colorado, 80218-1237, United States

Location

Florida Cancer Specialists & Res Inst

Fort Myers, Florida, 33901, United States

Location

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

St. Petersburg, Florida, 33705, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205-2005, United States

Location

University of Kentucky UK Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Tulane Cancer Center Clinic - Oncology

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Medical Center-Greenebaum Cancer Ctr

Baltimore, Maryland, 21201, United States

Location

John Hopkins Medicine - Hematology/oncology

Baltimore, Maryland, 21287, United States

Location

Maryland Oncology Hematology

Clinton, Maryland, 20735, United States

Location

Dana-Farber Cancer Institute - Medicine

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59102-6746, United States

Location

Oncology Hematology West PC dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Memorial Sloan Kettering Cancer Center - Monmouth - Oncology

Middletown, New Jersey, 07748-3052, United States

Location

University of New Mexico - Comprehensive Cancer Center

Albuquerque, New Mexico, 87131-0001, United States

Location

Roswell - Roswell Park Cancer Institute - Medical Oncology

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center - Westchester

East White Plains, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center - Nassau

Uniondale, New York, 11553, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195-0001, United States

Location

Lehigh Valley Physician Group

Allentown, Pennsylvania, 18103-6218, United States

Location

Allegheny General Hospital (AGH)

Pittsburgh, Pennsylvania, 15212-4756, United States

Location

UH Cleveland Medical Center

Columbia, South Carolina, 29210, United States

Location

Chattanooga Oncology and Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology - Central Austin Cancer Center

Austin, Texas, 78731, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

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

San Antonio, Texas, 78240, United States

Location

University Of Washington - Medical Center

Seattle, Washington, 98109, United States

Location

Northwest Medical Specialties PLLC

Tacoma, Washington, 98405-5016, United States

Location

Centro Oncológico Korben

Buenos Aires, Ciudad Autónoma de Buenos Aire, C1280AEB, Argentina

Location

Clínica Viedma

Viedma, Río Negro Province, R8500JYJ, Argentina

Location

Centro Oncologico de Rosario

Rosario, Santa Fe Province, S2000KZE, Argentina

Location

Centro para la Atención Integral del paciente Oncológico

San Miguel de Tucumán, Tucumán Province, T4000GTB, Argentina

Location

Liverpool Hospital Cancer Therapy Centre

Liverpool, New South Wales, 2170, Australia

Location

Mater Misericordiae Limited

Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Sunshine Hospital

Geelong, Victoria, 3220, Australia

Location

ZNA Jan Palfijn

Merksen, Antwerpen, 2170, Belgium

Location

Institut Jules Bordet - Oncologie Médicale

Anderlecht, Brussels Capital, 1070, Belgium

Location

Jessa Ziekenhuis - Campus Virga Jesse - Medische Oncologie

Hasselt, Limburg, 3500, Belgium

Location

UZ Gent - Medische Oncologie

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

CHU Brugmann - Victor Horta

Brussels, 1020, Belgium

Location

AZ Groeninge - Campus Kennedylaan

Kortrijk, 8500, Belgium

Location

Centro Gaucho Integrado de Onc

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Universidade Estadual de Campi

Campinas, São Paulo, 13083-970, Brazil

Location

Instituto Brasileiro de Controle do Cancer - ibcc

São Paulo, São Paulo, 03102-002, Brazil

Location

Hospital Nossa Senhora da Conc

Porto Alegre, 90610-000, Brazil

Location

Pontificia Universidade

Porto Alegre, 90610-000, Brazil

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

BC Cancer - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Sunnybrook Research Institute, sunnybrook Health Sciences Ct

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

ACEREY Centro de Investigación Clínica Oncológica

Viña del Mar, Región de Valparaíso, 2520612, Chile

Location

Centro de Estudios Clinicos In

Santiago, Región Metropolitana de Santia, 8420383, Chile

Location

Centro de Estudios Clínicos SAGA SpA

Santiago, Región Metropolitana de Santia, Chile

Location

Meditek Ltda.

Santiago, Santiago Metropolitan, 8420383, Chile

Location

University Hospital Brno

Brno, Brno-město, 625 00, Czechia

Location

Fakultni Thomayerova nemocnice

Prague, Praha 4, 140 59, Czechia

Location

FN Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

FN Kralovske Vinohrady

Prague, 100 34, Czechia

Location

Institut de cancérologie de Strasbourg Europe - ICANS

Strasbourg, Alsace, 67200, France

Location

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

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Institut Paoli Calmettes - Hôpital de jour

Marseille, Bouches-du-Rhône, 13273, France

Location

Hopital Saint-Andre - Service d'Oncologie Medicale

Bordeaux, Gironde, 33075, France

Location

Hopital Foch

Suresnes, Hauts-de-Seine, 92151, France

Location

CHU Michallon - Hopital Nord - Cancérologie Et Hématologie

Grenoble, Isère, 38043, France

Location

Hôpital privé Le Bois

Lille, Nord, 59000, France

Location

Centre Hospitalier de Poitiers

Poitiers, Poitou-Charentes, 86021, France

Location

Centre Leon Berard - departement d'oncologie medicale

Lyon, Rhône, 69373, France

Location

Clinique Victor Hugo - Hematologie

Le Mans, Sarthe, 72000, France

Location

CHD Vendee La Roche sur Yon - Gastro-Entérologie

La Roche-sur-Yon, 85925, France

Location

Centre de Lutte Contre le Cancer (CLCC)

Nice, 06189, France

Location

ICO - Site Rene Gauducheau - Oncologie Medicale

Saint-Herblain, 44805, France

Location

Hopital Trousseau - medical oncology

Tours, 37044, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54511, France

Location

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

Villejuif, Île-de-France Region, 94805, France

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Ospedale S.Donato, AUSL 8 di Arezzo

Arezzo, Arezzo, 52100, Italy

Location

Azienda Mater Domini

Catanzaro, Catanzaro, 88100, Italy

Location

P.O. Ss. Annunziata

Chieti Scalo, Chieti, 66013, Italy

Location

IRST

Meldola (Fc), Forli, 47014, Italy

Location

European Institute of Oncology

Milan, Milano, 20141, Italy

Location

IRCCS Policlinico San Matteo

Pavia, Pavia, 27100, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Roma, '00168, Italy

Location

AO S.Camillo-Forlanini

Roma, Roma, 00152, Italy

Location

Azienda Ospedaliera Santa Maria di Terni

Terni, Terni, 05100, Italy

Location

PO di Cremona, ASST di Cremona - Oncologia medica

Cremona, Italy

Location

AOUC Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

IRCCS Fondazione "Giovanni Pas

Napoli, 80131, Italy

Location

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Tlalpan, 14080, Mexico

Location

Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu

Poznan, Greater Poland Voivodeship, 60-569, Poland

Location

Szpital Specjalistyczny im. L. Rydygiera w Krakowie

Krakow, Lesser Poland Voivodeship, 31-826, Poland

Location

Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina

Otwock, Masovian Voivodeship, 05-400, Poland

Location

Szpital Specjalist. w Brzozowie,Podkarpacki Ośrodek Onkologi

Brzozów, Podkarpackie Voivodeship, 36-200, Poland

Location

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

Rzeszów, Podkarpackie Voivodeship, 35-021, Poland

Location

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

Gdansk, Pomeranian Voivodeship, 80-219, Poland

Location

Wojewodzki Szpital Specjalistyczny

Biała Podlaska, 21-500, Poland

Location

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych

Warsaw, 02-507, Poland

Location

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

Warsaw, 02-781, Poland

Location

Hospital Particular do Algarve - Gambelas-Faro

Faro, Faro District, 8005-226, Portugal

Location

H. Prof. Doutor Fernando Fonseca

Amadora, Lisbon District, 2720-276, Portugal

Location

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

Lisbon, Lisbon District, 1649-035, Portugal

Location

H. Santo Antonio. Centro Hospitalar do Porto

Porto, Porto District, 4099-001, Portugal

Location

Instituto Português Oncologia Francisco Gentil do Porto

Porto, 4200-072, Portugal

Location

H.G.U. de Elche

Elche, Alicante, 03203, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07010, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'

Barcelona, Barcelona, 08035, Spain

Location

Institut Catalá d´Oncología (I.C.O.)

Barcelona, Barcelona, 08908, Spain

Location

Hospital Del Mar

Barcelona, Barcelona, 8003, Spain

Location

Hospital Universitari Parc Tau

Sabadell, Barcelona, 8208, Spain

Location

ICO-Hospital Universitari de G

Girona, Girona, 17007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

Hospital U. 12 Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Universitario Virgen

Seville, Sevilla, 41009, Spain

Location

Fundación Instituto Valenciano

Valencia, Valencia, 46009, Spain

Location

Hospital Universitario Y Politécnico La Fe

Valencia, Valenciana, Comunidad, 46026, Spain

Location

C.H.U. de Orense

Ourense, 32005, Spain

Location

Addenbrooke's Hospital - Oncology

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Mount Vernon Cancer Centre

Northwood, England, HA6 2JW, United Kingdom

Location

Royal Blackburn Hospital - Oncology

Preston, Lancashire, PR2 9HT, United Kingdom

Location

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, London, City of, W6 8RF, United Kingdom

Location

The Christie NHS Foundation Trust - Medical Oncology

Manchester, Manchester, M20 4BX, United Kingdom

Location

Royal Marsden - Sutton

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

New Cross Hospital

Wolverhampton, Wolverhampton, WV10 0QP, United Kingdom

Location

Royal Derby Hospital

Derby, DE22 3NE, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 39284329 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; Disease Progression

Interventions

tivozanib; Nivolumab

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: July 23, 2021
• First Posted: August 3, 2021
• Study Start: September 9, 2021
• Primary Completion: September 30, 2025
• Study Completion: December 30, 2025
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4); ES (16); CL (4); AU (4); US (36); AR (4); ME (1); BE (6); BR (6); CZ (4); PT (5); IT (12); FR (16); PL (9); GB (10); DE (2)