Clinical trial NCT04987203: Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Renal Cell Carcinoma
Keywords: Immune Checkpoint Inhibitor
Open-label
Monotherapy
Disease Progression
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
name: Bristol-Myers Squibb
First posted: 2021-08-03
Enrollment: 343
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival
timeFrame: Until progressive disease [PD] (Approximately 30 months)
Secondary outcomes:
measure: Overall Survival
timeFrame: From Screening (Days -28 to -1) until death (Approximately 42 months)
measure: Progression free survival
timeFrame: Until progressive disease [PD] (Approximately 30 months)
measure: Objective Response Rate
timeFrame: From Screening (Days -28 to -1) until PD (Approximately 30 months)
measure: Duration of Response
timeFrame: From Screening (Days -28 to -1) until PD or death (Approximately 30 months)
measure: Number of subjects with serious and non-serious adverse events
timeFrame: From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Irvine
country: United States
facility: Chao Family Comprehensive Cancer Center, UC Irvine
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Redwood City
country: United States
facility: Leland Stanford Junior University
state: California
city: Riverside
country: United States
facility: Kaiser Permanente Riverside Medical Center
state: California
city: Denver
country: United States
facility: US Oncology - Rocky Mountain Cancer Centers - Midtown
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists & Res Inst
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists & Research Institute (FCS) - Tampa Cancer Center Location
state: Florida
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky UK Markey Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Cancer Center Clinic - Oncology
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center-Greenebaum Cancer Ctr
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins Medicine - Hematology/oncology
state: Maryland
city: Clinton
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute - Medicine
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Omaha
country: United States
facility: Oncology Hematology West PC dba Nebraska Cancer Specialists
state: Nebraska
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center - Monmouth - Oncology
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico - Comprehensive Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell - Roswell Park Cancer Institute - Medical Oncology
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center - Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Cancer Center - Nassau
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Physician Group
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital (AGH)
state: Pennsylvania
city: Columbia
country: United States
facility: UH Cleveland Medical Center
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Central Austin Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: San Antonio
country: United States
facility: US Oncology Texas Oncology (CCC of South Texas) - San Antonio Medical Center
state: Texas
city: Seattle
country: United States
facility: University Of Washington - Medical Center
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties PLLC
state: Washington
city: Buenos Aires
country: Argentina
facility: Centro Oncológico Korben
state: Ciudad Autónoma De Buenos Aire
city: Viedma
country: Argentina
facility: Clínica Viedma
state: Río Negro
city: Rosario
country: Argentina
facility: Centro Oncologico de Rosario
state: Santa Fe
city: San Miguel de Tucumán
country: Argentina
facility: Centro para la Atención Integral del paciente Oncológico
state: Tucumán
city: Liverpool
country: Australia
facility: Liverpool Hospital Cancer Therapy Centre
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Misericordiae Limited
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Geelong
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Merksen
country: Belgium
facility: ZNA Jan Palfijn
state: Antwerpen
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet - Oncologie Médicale
state: Brussels Capital Region
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse - Medische Oncologie
state: Limburg
city: Gent
country: Belgium
facility: UZ Gent - Medische Oncologie
state: Oost-Vlaanderen
city: Bruxelles
country: Belgium
facility: CHU Brugmann - Victor Horta
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus Kennedylaan
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado de Onc
state: Rio Grande Do Sul
city: Itajai
country: Brazil
facility: Clinica de Neoplasias Litoral
state: Santa Catarina
city: Campinas
country: Brazil
facility: Universidade Estadual de Campi
state: São Paulo
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conc
city: Porto Alegre
country: Brazil
facility: Pontificia Universidade
city: São Paulo
country: Brazil
facility: Instituto Brasileiro de Controle do Cancer - ibcc
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer - Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Research Institute, sunnybrook Health Sciences Ct
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Princess Margaret Cancer Centre
state: Ontario
city: Santiago de Chile
country: Chile
facility: Meditek Ltda.
state: Región Metropolitana De Santiago
city: Santiago
country: Chile
facility: Centro de Estudios Clinicos In
state: Región Metropolitana De Santia
city: Santiago
country: Chile
facility: Centro de Estudios Clínicos SAGA SpA
state: Región Metropolitana De Santia
city: Viña del mar
country: Chile
facility: ACEREY Centro de Investigación Clínica Oncológica
state: Valparaíso
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove
city: Praha 10
country: Czechia
facility: FN Kralovske Vinohrady
city: Praha 4
country: Czechia
facility: Fakultni Thomayerova nemocnice
city: Strasbourg
country: France
facility: Institut de cancérologie de Strasbourg Europe - ICANS
state: Alsace
city: Marseille
country: France
facility: Institut Paoli Calmettes - HÃ´pital de jour
state: Bouches-du-Rhône
city: Bordeaux
country: France
facility: Hopital Saint-Andre - Service d'Oncologie Medicale
state: Gironde
city: Suresnes
country: France
facility: Hopital Foch
state: Hauts-de-Seine
city: Grenoble
country: France
facility: CHU Michallon - Hopital Nord - Cancérologie Et Hématologie
state: Isère
city: Lille
country: France
facility: Hôpital privé Le Bois
state: Nord
city: Poitiers
country: France
facility: Centre Hospitalier de Poitiers
state: Poitou-Charentes
city: Pierre-Bénite
country: France
facility: Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
state: Rhône-Alpes
city: Lyon
country: France
facility: Centre Leon Berard - departement d'oncologie medicale
state: Rhône
city: Le Mans
country: France
facility: Clinique Victor Hugo - Hematologie
state: Sarthe
city: La Roche-sur-Yon
country: France
facility: CHD Vendee La Roche sur Yon - Gastro-Entérologie
city: Nice
country: France
facility: Centre de Lutte Contre le Cancer (CLCC)
city: St Herblain
country: France
facility: ICO - Site Rene Gauducheau - Oncologie Medicale
city: Tours
country: France
facility: Hopital Trousseau - medical oncology
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Centre de Lutte Contre le Cancer (CLCC) - Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
state: Île-de-France
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Chieti Scalo
country: Italy
facility: P.O. Ss. Annunziata
state: Chieti
city: Meldola (Fc)
country: Italy
facility: IRST
state: Forli
city: Arezzo
country: Italy
facility: Ospedale S.Donato, AUSL 8 di Arezzo
city: Catanzaro
country: Italy
facility: Azienda Mater Domini
city: Cremona
country: Italy
facility: PO di Cremona, ASST di Cremona - Oncologia medica
city: Firenze
country: Italy
facility: AOUC Azienda Ospedaliero-Universitaria Careggi
city: Milano
country: Italy
facility: European Institute of Oncology
city: Napoli
country: Italy
facility: IRCCS Fondazione "Giovanni Pas
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Roma
country: Italy
facility: AO S.Camillo-Forlanini
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Tlalpan
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. L. Rydygiera w Krakowie
state: Malopolskie
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina
state: Mazowieckie
city: Brzozow
country: Poland
facility: Szpital Specjalist. w Brzozowie,Podkarpacki Ośrodek Onkologi
state: Podkarpackie
city: Rzeszow
country: Poland
facility: Nzoz Mrukmed Lekarz Beata Madej-Mruk I Partner Sp. P.
state: Podkarpackie
city: Gdańsk
country: Poland
facility: COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii
state: Pomorskie
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu
state: Wielkopolskie
city: Biala Podlaska
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Amadora
country: Portugal
facility: H. Prof. Doutor Fernando Fonseca
state: Lisboa
city: Faro
country: Portugal
facility: Hospital Particular do Algarve - Gambelas-Faro
city: Lisboa
country: Portugal
facility: H. de Santa Maria. Centro Hospitalar Lisboa Norte - Oncologia
city: Porto
country: Portugal
facility: H. Santo Antonio. Centro Hospitalar do Porto
city: Porto
country: Portugal
facility: Instituto Português Oncologia Francisco Gentil do Porto
city: Elche
country: Spain
facility: H.G.U. de Elche
state: Alicante
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Baleares
city: Sabadell
country: Spain
facility: Hospital Universitari Parc Tau
state: Barcelona
city: Valencia
country: Spain
facility: Hospital Universitario Y Politécnico La Fe
state: Valenciana, Comunidad
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'
city: Barcelona
country: Spain
facility: Institut Catalá d´Oncología (I.C.O.)
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Girona
country: Spain
facility: ICO-Hospital Universitari de G
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital U. 12 Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Orense
country: Spain
facility: C.H.U. de Orense
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital - Oncology
state: Cambridgeshire
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: England
city: Preston
country: United Kingdom
facility: Royal Blackburn Hospital - Oncology
state: Lancashire
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust - Hammersmith Hospital
state: London, City Of
city: Sutton
country: United Kingdom
facility: Royal Marsden - Sutton
state: Surrey
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust - Medical Oncology
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
References:
citation: 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.