Fotivda (tivozanib)

P3, N=343, Completed, AVEO Pharmaceuticals, Inc. | Active, not recruiting --> Completed | Trial primary completion date: Sep 2025 --> Jan 2026

Curcumin did not sensitize HepG2-DR cells to doxorubicin, whereas verapamil and simvastatin enhanced doxorubicin cytotoxicity only at toxic concentrations. In contrast, several TKIs, including nilotinib, tivozanib, and, to a lesser extent, cabozantinib, exhibited synergistic effects with doxorubicin in HepG2-DR cells...Third-generation MDR1 inhibitors (tariquidar, elacridar, and zosuquidar) sensitized HepG2-DR and HB-303 cells at non-toxic nanomolar concentrations in vitro...MDR1 inhibitors, such as zosuquidar, may enable dose reductions of chemotherapeutic agents, whereas the use of synergistic TKIs, such as tivozanib, may improve therapeutic outcomes and minimize adverse effects in children with HB. TG100-115, a TRPM7 kinase inhibitor, provides neuroprotection and attenuates NLRP3 inflammasome-mediated neuroinflammation in a neonatal mouse model of hypoxic-ischemic brain injury.

P1/2, N=31, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2029 | Trial primary completion date: Dec 2026 --> Dec 2028

P1/2, N=29, Suspended, University of Florida | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=35, Not yet recruiting, City of Hope Medical Center

Drug sensitivity analysis identified compounds such as sotrastaurin (-10.2 kcal/mol), austocystin D (-9.7 kcal/mol), and tivozanib (-9.3 kcal/mol) as potentially effective inhibitors based on predicted binding affinity. Our integrative analysis highlights HTR1F as a potential biomarker associated with prognosis, immune modulation, and drug sensitivity across multiple cancer types. These findings provide a foundation for future experimental and clinical studies to explore HTR1F-targeted therapies.

P3, N=343, Active, not recruiting, AVEO Pharmaceuticals, Inc. | Trial completion date: Jul 2026 --> Dec 2025 | Trial primary completion date: Apr 2024 --> Sep 2025

Clinically, FAHD1 overexpression correlated with poor prognosis, validated through functional assays showing its knockdown suppressed proliferation, invasion, and migration in HCC models. An FAHD1-derived risk score (FRS) robustly stratifies patient prognosis and predicts responsiveness to immunotherapy, while molecular docking highlighted tivozanib as a potential FAHD1-targeting agent.

P2, N=5, Terminated, Massachusetts General Hospital | Active, not recruiting --> Terminated; Slow accrual

P1/2, N=29, Recruiting, University of Florida | Trial primary completion date: Jun 2025 --> Dec 2025

Mechanistically, tivozanib induced cell state transition from MITFlow to MITFhigh state via VEGFR2 inhibition followed by NF-κB pathway activation, restoring MITF transcriptional activity and growth dependency. The combination of tivozanib and TT-012 synergistically inhibited melanoma growth both in vitro and in vivo, underscoring its potential as a novel therapeutic strategy for BRAFWT melanoma.

Identifying plasma TKI levels associated with efficacy and reduced toxicity could minimize under- or overdosing, improving outcomes and quality of life. TDM may allow dose adjustments early in therapy, improving therapeutic management and reducing healthcare costs. Findings may also inform treatment of other cancers using TKIs or TKI-immunotherapy combinations. The trial (clinicaltrials.gov NCT04659343) is expected to conclude in 2028, with results in 2029.