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

Official 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).

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 130 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 343 participants

Study Arms

• 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.
• 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.

Interventions

• DRUG: Tivozanib — Tivozanib will be administered orally.
• DRUG: Nivolumab — Nivolumab will be administered via intravenous infusion.

Primary Outcomes

• Progression free survival (Until progressive disease [PD] (Approximately 30 months))

Secondary Outcomes

• 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))

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.

Trial Locations

• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• Chao Family Comprehensive Cancer Center, UC Irvine, Irvine, California, United States
• University of California San Diego, La Jolla, California, United States
• Leland Stanford Junior University, Redwood City, California, United States
• Kaiser Permanente Riverside Medical Center, Riverside, California, United States
• US Oncology - Rocky Mountain Cancer Centers - Midtown, Denver, Colorado, United States
• Florida Cancer Specialists & Res Inst, Fort Myers, Florida, United States
• Florida Cancer Specialists & Research Institute (FCS) - Tampa Cancer Center Location, St. Petersburg, Florida, United States
• The University of Kansas Cancer Center, Westwood, Kansas, United States
• University of Kentucky UK Markey Cancer Center, Lexington, Kentucky, United States
• ...and 10 more locations

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