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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04987203
Recruitment Status : Recruiting
First Posted : August 3, 2021
Last Update Posted : June 9, 2023
Sponsor:
Collaborators:
Parexel
Bristol-Myers Squibb
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.

Study Description
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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).

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Tivozanib Drug: Nivolumab Phase 3

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. A Safety Follow-up Visit will be performed 30 days (± 7 days) after the last dose of study drug.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 326 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 9, 2021
Estimated Primary Completion Date : August 1, 2024
Estimated Study Completion Date : August 1, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Tivozanib
Tivozanib will be administered orally.

Drug: Nivolumab
Nivolumab will be administered via intravenous infusion.
Experimental: 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.
 Drug: Tivozanib
Tivozanib will be administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: From Screening (Days -28 to -1) until death (Approximately 42 months) ]
    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.

  2. Objective Response Rate [ Time Frame: From Screening (Days -28 to -1) until PD (Approximately 30 months) ]
    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.

  3. Duration of Response [ Time Frame: From Screening (Days -28 to -1) until PD or death (Approximately 30 months) ]
    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.

  4. 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) ]
    Assessment of the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04987203


Contacts
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Contact: AVEO Clinical Trials Office (857) 400-0101 clinical@aveooncology.com

Locations
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Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
Parexel
Bristol-Myers Squibb
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04987203    
Other Study ID Numbers: AV-951-20-304
First Posted: August 3, 2021    Key Record Dates
Last Update Posted: June 9, 2023
Last Verified: June 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AVEO Pharmaceuticals, Inc.:
Immune Checkpoint Inhibitor
Open-label
Monotherapy
Disease Progression
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
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
Nivolumab
Tivozanib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors