Renal Cell CarcinomaPhase 3NCT04987203
Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma
A Phase 3 study testing Tivozanib and Nivolumab in people with Renal Cell Carcinoma, run by AVEO Pharmaceuticals, Inc. at 139 sites in 16 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Tivozanib and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 343 participants
- Where
- 139 sitesin 16 countries
- Study dates
- 9 Sep 2021to 20 Jan 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
139 sites in 16 countries.
139 sites in 16 countries
United States36 sites
University of New Mexico - Comprehensive Cancer Center
Albuquerque, New Mexico, 87131-0001
Lehigh Valley Physician Group
Allentown, Pennsylvania, 18103-6218
Texas Oncology - Central Austin Cancer Center
Austin, Texas, 78731
University of Maryland Medical Center-Greenebaum Cancer Ctr
Baltimore, Maryland, 21201
John Hopkins Medicine - Hematology/oncology
Baltimore, Maryland, 21287
St. Vincent Frontier Cancer Center
Billings, Montana, 59102-6746
Dana-Farber Cancer Institute - Medicine
Boston, Massachusetts, 02215
Roswell - Roswell Park Cancer Institute - Medical Oncology
Buffalo, New York, 14263
Chattanooga Oncology and Hematology Associates
Chattanooga, Tennessee, 37404
Cleveland Clinic
Cleveland, Ohio, 44195-0001
Maryland Oncology Hematology
Clinton, Maryland, 20735
UH Cleveland Medical Center
Columbia, South Carolina, 29210
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
US Oncology - Rocky Mountain Cancer Centers - Midtown
Denver, Colorado, 80218-1237
Henry Ford Hospital
Detroit, Michigan, 48202
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Memorial Sloan Kettering Cancer Center - Westchester
East White Plains, New York, 10604
Florida Cancer Specialists & Res Inst
Fort Myers, Florida, 33901
Chao Family Comprehensive Cancer Center, UC Irvine
Irvine, California, 92868
University of California San Diego
La Jolla, California, 92037
University of Kentucky UK Markey Cancer Center
Lexington, Kentucky, 40536
Memorial Sloan Kettering Cancer Center - Monmouth - Oncology
Middletown, New Jersey, 07748-3052
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Tulane Cancer Center Clinic - Oncology
New Orleans, Louisiana, 70112
Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital
New York, New York, 10065
Oncology Hematology West PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Allegheny General Hospital (AGH)
Pittsburgh, Pennsylvania, 15212-4756
Leland Stanford Junior University
Redwood City, California, 94063
Kaiser Permanente Riverside Medical Center
Riverside, California, 92505
US Oncology Texas Oncology (CCC of South Texas) - San Antonio Medical Center
San Antonio, Texas, 78240
University Of Washington - Medical Center
Seattle, Washington, 98109
Florida Cancer Specialists & Research Institute (FCS) - Tampa Cancer Center Location
St. Petersburg, Florida, 33705
Northwest Medical Specialties PLLC
Tacoma, Washington, 98405-5016
Memorial Sloan Kettering Cancer Center - Nassau
Uniondale, New York, 11553
The University of Kansas Cancer Center
Westwood, Kansas, 66205-2005
France16 sites
Hopital Saint-Andre - Service d'Oncologie Medicale
Bordeaux, Gironde, 33075
CHU Michallon - Hopital Nord - Cancérologie Et Hématologie
Grenoble, Isère, 38043
CHD Vendee La Roche sur Yon - Gastro-Entérologie
La Roche-sur-Yon, 85925
Clinique Victor Hugo - Hematologie
Le Mans, Sarthe, 72000
Hôpital privé Le Bois
Lille, Nord, 59000
Centre Leon Berard - departement d'oncologie medicale
Lyon, Rhône, 69373
Institut Paoli Calmettes - Hôpital de jour
Marseille, Bouches-du-Rhône, 13273
Centre de Lutte Contre le Cancer (CLCC)
Nice, 06189
Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495
Centre Hospitalier de Poitiers
Poitiers, Poitou-Charentes, 86021
ICO - Site Rene Gauducheau - Oncologie Medicale
Saint-Herblain, 44805
Institut de cancérologie de Strasbourg Europe - ICANS
Strasbourg, Alsace, 67200
Hopital Foch
Suresnes, Hauts-de-Seine, 92151
Hopital Trousseau - medical oncology
Tours, 37044
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, 54511
Centre de Lutte Contre le Cancer (CLCC) - Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
Villejuif, Île-de-France Region, 94805
Spain16 sites
Hospital de La Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
Hospital Universitario Vall d'
Barcelona, Barcelona, 08035
Institut Catalá d´Oncología (I.C.O.)
Barcelona, Barcelona, 08908
Hospital Del Mar
Barcelona, Barcelona, 8003
H.G.U. de Elche
Elche, Alicante, 03203
ICO-Hospital Universitari de G
Girona, Girona, 17007
Hospital Universitario Ramón y Cajal
Madrid, Madrid, 28034
Hospital Clínico San Carlos
Madrid, Madrid, 28040
Hospital U. 12 Octubre
Madrid, Madrid, 28041
Hospital Universitario La Paz
Madrid, Madrid, 28046
C.H.U. de Orense
Ourense, 32005
Hospital Universitario Son Espases
Palma de Mallorca, Balearic Islands, 07010
Hospital Universitari Parc Tau
Sabadell, Barcelona, 8208
Hospital Universitario Virgen
Seville, Sevilla, 41009
Fundación Instituto Valenciano
Valencia, Valencia, 46009
Hospital Universitario Y Politécnico La Fe
Valencia, Valenciana, Comunidad, 46026
Italy12 sites
Ospedale S.Donato, AUSL 8 di Arezzo
Arezzo, Arezzo, 52100
Azienda Mater Domini
Catanzaro, Catanzaro, 88100
P.O. Ss. Annunziata
Chieti Scalo, Chieti, 66013
PO di Cremona, ASST di Cremona - Oncologia medica
Cremona
AOUC Azienda Ospedaliero-Universitaria Careggi
Florence, 50134
IRST
Meldola (Fc), Forli, 47014
European Institute of Oncology
Milan, Milano, 20141
IRCCS Fondazione "Giovanni Pas
Naples, 80131
IRCCS Policlinico San Matteo
Pavia, Pavia, 27100
Fondazione Policlinico Universitario Agostino Gemelli
Roma, Roma, '00168
AO S.Camillo-Forlanini
Roma, Roma, 00152
Azienda Ospedaliera Santa Maria di Terni
Terni, Terni, 05100
United Kingdom10 sites
Addenbrooke's Hospital - Oncology
Cambridge, Cambridgeshire, CB2 0QQ
Royal Derby Hospital
Derby, DE22 3NE
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
Imperial College Healthcare NHS Trust - Hammersmith Hospital
London, London, City of, W6 8RF
The Christie NHS Foundation Trust - Medical Oncology
Manchester, Manchester, M20 4BX
Mount Vernon Cancer Centre
Northwood, England, HA6 2JW
Royal Blackburn Hospital - Oncology
Preston, Lancashire, PR2 9HT
Royal Marsden - Sutton
Sutton, Surrey, SM2 5PT
Royal Marsden Hospital
Sutton, Surrey, SM2 5PT
New Cross Hospital
Wolverhampton, Wolverhampton, WV10 0QP
Poland9 sites
Wojewodzki Szpital Specjalistyczny
Biała Podlaska, 21-500
Szpital Specjalist. w Brzozowie,Podkarpacki Ośrodek Onkologi
Brzozów, Podkarpackie Voivodeship, 36-200
COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii
Gdansk, Pomeranian Voivodeship, 80-219
Szpital Specjalistyczny im. L. Rydygiera w Krakowie
Krakow, Lesser Poland Voivodeship, 31-826
Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina
Otwock, Masovian Voivodeship, 05-400
Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu
Poznan, Greater Poland Voivodeship, 60-569
Nzoz Mrukmed Lekarz Beata Madej-Mruk I Partner Sp. P.
Rzeszów, Podkarpackie Voivodeship, 35-021
Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych
Warsaw, 02-507
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, 02-781
Belgium6 sites
Institut Jules Bordet - Oncologie Médicale
Anderlecht, Brussels Capital, 1070
CHU Brugmann - Victor Horta
Brussels, 1020
UZ Gent - Medische Oncologie
Ghent, Oost-Vlaanderen, 9000
Jessa Ziekenhuis - Campus Virga Jesse - Medische Oncologie
Hasselt, Limburg, 3500
AZ Groeninge - Campus Kennedylaan
Kortrijk, 8500
ZNA Jan Palfijn
Merksen, Antwerpen, 2170
Brazil6 sites
Universidade Estadual de Campi
Campinas, São Paulo, 13083-970
Clinica de Neoplasias Litoral
Itajaí, Santa Catarina, 88301-220
Centro Gaucho Integrado de Onc
Porto Alegre, Rio Grande do Sul, 90110-270
Hospital Nossa Senhora da Conc
Porto Alegre, 90610-000
Pontificia Universidade
Porto Alegre, 90610-000
Instituto Brasileiro de Controle do Cancer - ibcc
São Paulo, São Paulo, 03102-002
Portugal5 sites
H. Prof. Doutor Fernando Fonseca
Amadora, Lisbon District, 2720-276
Hospital Particular do Algarve - Gambelas-Faro
Faro, Faro District, 8005-226
H. de Santa Maria. Centro Hospitalar Lisboa Norte - Oncologia
Lisbon, Lisbon District, 1649-035
H. Santo Antonio. Centro Hospitalar do Porto
Porto, Porto District, 4099-001
Instituto Português Oncologia Francisco Gentil do Porto
Porto, 4200-072
Argentina4 sites
Centro Oncológico Korben
Buenos Aires, Ciudad Autónoma de Buenos Aire, C1280AEB
Centro Oncologico de Rosario
Rosario, Santa Fe Province, S2000KZE
Centro para la Atención Integral del paciente Oncológico
San Miguel de Tucumán, Tucumán Province, T4000GTB
Clínica Viedma
Viedma, Río Negro Province, R8500JYJ
Australia4 sites
Mater Misericordiae Limited
Brisbane, Queensland, 4101
Sunshine Hospital
Geelong, Victoria, 3220
Liverpool Hospital Cancer Therapy Centre
Liverpool, New South Wales, 2170
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Canada4 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Sunnybrook Research Institute, sunnybrook Health Sciences Ct
Toronto, Ontario, M4N 3M5
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
BC Cancer - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6
Chile4 sites
Centro de Estudios Clinicos In
Santiago, Región Metropolitana de Santia, 8420383
Centro de Estudios Clínicos SAGA SpA
Santiago, Región Metropolitana de Santia
Meditek Ltda.
Santiago, Santiago Metropolitan, 8420383
ACEREY Centro de Investigación Clínica Oncológica
Viña del Mar, Valparaiso, 2520612
Czechia4 sites
University Hospital Brno
Brno, Brno-město, 625 00
FN Hradec Kralove
Hradec Králové, 500 05
Fakultni Thomayerova nemocnice
Prague, Praha 4, 140 59
FN Kralovske Vinohrady
Prague, 100 34
Germany2 sites
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Mexico1 site
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Tlalpan, 14080
About this study
Official title: TiNivo-2: A Phase 3, Randomized, Controlled, Multicenter, Open-label Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Who Have Progressed Following One or Two Lines of Therapy Where One Line Has an Immune Checkpoint Inhibitor
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).
Read the detailed description
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
- Renal Cell Carcinoma
- Being tested
- Tivozanib, Nivolumab
- Keywords
- Immune Checkpoint Inhibitor, Open-label, Monotherapy, Disease Progression
- Medical subject headings
- Carcinoma, Renal Cell, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TivozanibDrug
Tivozanib will be administered orally.
NivolumabDrug
Nivolumab will be administered via intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Tivozanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Until progressive disease [PD] (Approximately 30 months)
Secondary outcomes (5)
Overall Survival
Comparsion of the OS of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. OS is defined as the time from the date of randomization to date of death due to any cause.
Measured: From Screening (Days -28 to -1) until death (Approximately 42 months)
Progression free survival
PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to RECIST, or death due to any reasons whichever comes first. PFS as assessed by investigator.
Measured: Until progressive disease [PD] (Approximately 30 months)
Objective Response Rate
Comparison of ORR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. ORR is defined as the proportion of subjects with confirmed complete response or confirmed partial response according to RECIST relative to the total population of randomized subjects.
Measured: From Screening (Days -28 to -1) until PD (Approximately 30 months)
Duration of Response
Comparison of DoR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. DoR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause.
Measured: From Screening (Days -28 to -1) until PD or death (Approximately 30 months)
Number of subjects with serious and non-serious adverse events
Assessment of the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib.
Measured: From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start9 Sep 2021
- Primary completion20 Jan 2026
- Study completion20 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 343 participants (actual)
Sponsor and investigators
- Lead sponsor
- AVEO Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel, Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04987203
- Sponsor's protocol ID
- AV-951-20-304
- Status last verified
- May 2026
- First submitted
- 23 Jul 2021
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 39284329Yang 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.
PubMed 35304832
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TiNivo-2: A Phase 3, Randomized, Controlled, Multicenter, Open-label Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Who Have Progressed Following One or Two Lines of Therapy Where One Line Has an Immune Checkpoint Inhibitor
- ClinicalTrials.gov ID
- NCT04987203
- Acronym / sponsor ID
- AV-951-20-304
- Conditions
- Renal Cell Carcinoma
- Keywords
- Immune Checkpoint Inhibitor, Open-label, Monotherapy, Disease Progression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 343 participants (actual)
- Lead sponsor
- AVEO Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Parexel, Bristol-Myers Squibb
- Study start
- 9 Sep 2021 (actual)
- Primary completion
- 20 Jan 2026 (actual)
- Study completion
- 20 Jan 2026 (actual)
- First posted
- 3 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tivozanib in Combination with Nivolumab | Experimental | Drug: Tivozanib, Drug: NivolumabSubjects 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. |
| Tivozanib | Experimental | Drug: TivozanibSubjects 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TivozanibTivozanib will be administered orally. | Drug | Tivozanib, Tivozanib in Combination with Nivolumab |
| NivolumabNivolumab will be administered via intravenous infusion. | Drug | Tivozanib in Combination with Nivolumab |
Primary outcome
Progression free survival
Time frame: Until progressive disease [PD] (Approximately 30 months)
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.
5 secondary outcomes
Overall Survival
Time frame: From Screening (Days -28 to -1) until death (Approximately 42 months)
Progression free survival
Time frame: Until progressive disease [PD] (Approximately 30 months)
Objective Response Rate
Time frame: From Screening (Days -28 to -1) until PD (Approximately 30 months)
Duration of Response
Time frame: From Screening (Days -28 to -1) until PD or death (Approximately 30 months)
Number of subjects with serious and non-serious adverse events
Time frame: From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Derived from this study: PubMed 39284329Choueiri 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.
- Derived from this study: PubMed 35304832Yang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
139 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tivozanib and Nivolumab in people with Renal Cell Carcinoma, run by AVEO Pharmaceuticals, Inc. at 139 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 139 sites in United States, France, Spain, Italy, United Kingdom and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: Until progressive disease [PD] (Approximately 30 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04987203, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.