Fotivda (tivozanib)

P3, N=1040, Not yet recruiting, Alliance for Clinical Trials in Oncology

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

Considering that resveratrol can increase the apoptosis of cancer cells alone and in combination with tivozanib and prevent the proliferation of cancer cells and also reduce the side effects of tivozanib, we suggest that resveratrol as a potential bioactive molecule can be used in treatment of kidney cancer should be used in combination with tivozanib.

P1/2, N=29, Recruiting, University of Florida | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025

These findings highlight the substantial anticancer potential of tivozanib in OSCC and thus its promise as a therapeutic option. Beyond reducing cell viability and inducing apoptosis, the capacity of tivozanib to inhibit EMT and modulate key proteins presents the possibility of a paradigm shift in OSCC treatment.

When the tumors have metastasized, systemic therapy with protein-tyrosine kinase antagonists including sorafenib, sunitinib, pazopanib, and tivozanib that target vascular endothelial, platelet-derived, fibroblast, hepatocyte, and stem cell factor growth factor receptors (VEGFR, PDGFR, FGFR, MET, and Kit) were prescribed after 2005. The monoclonal antibody immune checkpoint inhibitor nivolumab (targeting PD1) was approved for the treatment of RCCs in 2015. It is usually used now in combination with ipilimumab (targeting CTLA-4) or cabozantinib (a multikinase blocker). Other combination therapies include pembrolizumab (targeting programed cell death protein 1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors.

P1/2, N=29, Recruiting, University of Florida | Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Jan 2024 --> Dec 2024 | Suspended --> Recruiting

P2, N=48, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1/2, N=29, Suspended, University of Florida

P2, N=48, Not yet recruiting, M.D. Anderson Cancer Center | N=10 --> 48

P1/2, N=24, Recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

We included randomized controlled trials (RCTs) investigating the use of: cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib, cabozantinib + nivolumab, lenvatinib + pembrolizumab, axitinib + avelumab, and axitinib + pembrolizumab in previously untreated adult patients with metastatic clear cell RCC... The general safety profile, including common AEs, is better when TKIs are used as monotherapy vs. in combination with immunological agents. To confirm these findings, further research is needed, including large RCTs.

P1/2, N=29, Recruiting, University of Florida | Trial completion date: Dec 2024 --> Jun 2024

Various small drug molecule that targets the RTKs having the same scaffold, includes Lapatinib, Tivozanib, Erlotinib, Gefitinib, Crizotinib, and Ceritinib. Lapatinib is identified as a potential inhibitor for both the RTKs. Our study thus suggests the probable direction that could be further explored in inhibiting EGFR protein harboring breast cancer.

These data suggest comparable activity of tivozanib with the pivotal trial data and other TKIs in a real-world population. Its tolerability positions tivozanib as an attractive first-line option for those unsuitable for combination therapies or unable to tolerate other TKIs.

P1b/2, N=27, Terminated, AVEO Pharmaceuticals, Inc. | N=42 --> 27 | Active, not recruiting --> Terminated; The study was terminated due to regulatory approval of newer therapeutic options and slower than anticipated accrual.

P3, N=326, Active, not recruiting, AVEO Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

Tivozanib demonstrated activity and a favorable safety profile in patients with nccRCC. These data add to the body of evidence supporting the use of VEGFR-TKI in advanced nccRCC.

AngII type 1 receptor blockade by losartan prevented these consequences caused by tivozanib and kept blood pressure within normal range. The results showed that AngII and ET-1 might be potential targets in the clinical studies and management of hypertension induced by tivozanib.

Dexamethasone is commonly used in the management of cancer disease and thus coadministration with tivozanib therapy may cause treatment failure in patients. The simplicity, speed and cost-effectiveness of the reported methods are ideal for supporting in vivo and in vitro tivozanib studies, including drug-drug interaction studies, particularly in bioanalytical labs lacking LC-MS/MS capabilities.

We tabulated these and other properties of the FDA-approved kinase inhibitors. Of the 74 approved drugs, 30 fail to comply with the rule of five.

Overall response rates (ORR) were 9-25% with nivolumab (niv), 42% with niv + ipilimumab (ipi), 55.7% with niv + cabozantinib, 56% with niv + tivozanib vs. 5% with everolimus. ORR was 51.5-58% with avelumab + axitinib vs. 25.5% with sunitinib...ORR was 32-36% with atezolizumab + bevacizumab vs. 29-33% with sunitinib. In patients with PD-L1+ve and -ve ccRCC, niv, atezolizumab, ipi, and pembrolizumab were safe and effective alone and when combined with cabozantinib, tivozanib, axitinib, levantinib, and pegilodecakin...Pembrolizumab was safe and effective in preventing recurrence in ccRCC patients with nephrectomy. Additional randomized, double-blind, multicenter clinical trials are needed to confirm these results.

Durvalumab, a PD-L1 inhibitor, is part of an immunotherapeutic drug class shown to have prolonged survival benefit in patients with advanced stage hepatocellular carcinoma (HCC). Here, the design of and rationale for this trial in both treatment naive patients and those who progress on atezolizumab and bevacizumab for advanced or metastatic HCC are described. Clinical Trial Registration: NCT03970616.

P1/2, N=29, Recruiting, University of Florida | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2023 --> Dec 2023

Robust pre-clinical data and early, encouraging clinical data supports the utilization of tivozanib as a therapeutic agent for XPO7/SLK expressing CCA. Learning Objectives: Upon completion, participant will be able to discuss emerging biomarkers in cholangiocarcinoma. Upon completion, participant will be able to describe pre-clinical tool and clinical trials evaluating targeted therapies in cholangiocarcinoma.

This signal-seeking, single-arm, prospective clinical trial aims to determine the objective response of tivozanib and atezolizumab in advanced immunogenically cold solid tumors. Clinical Trial Registration: NCT05000294 (ClinicalTrials.gov).

The high risk-score group showed better response to ICI and could benefit from TKIs of axitinib, tivozanib, or sorafenib, preferentially in combination, whereas sunitinib and pazopanib would better fit the low risk-score group. Here we showed a six-gene ADCP signature that correlated with prognosis and immune modulation in ccRCC. The signature-based risk stratification was associated with response to both ICI and tyrosine kinase inhibition in ccRCC.

P1/2, N=29, Recruiting, University of Florida | Suspended --> Recruiting

P1/2, N=29, Suspended, University of Florida | Recruiting --> Suspended

Tivozanib showed good activity and favorable safety profile in a real-world cohort of unselected patients with mRCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC patients who could still receive a monotherapy with VEGFR inhibitors in the first line.

P1/2, N=29, Recruiting, University of Florida | Not yet recruiting --> Recruiting

P1/2, N=29, Not yet recruiting, University of Florida

Molecular array data resulted in identifying the specific and key players participating in cancer progression when the drug combination was used. The innovative combination of fluvoxamine and tivozanib reiterates the use of drug repositioning for precision medicine and subsequent companion diagnostic development.

A wide spectrum of treatment recommendations based on multiple decision criteria was demonstrated. Significant inter-expert variations were observed. This demonstrates how data from randomized trials are implemented differently when transferred into daily practice.

Although this study did not proceed to stage 2, there was an early efficacy signal with a very favourable toxicity profile. A phase 1/2 trial of tivozanib in combination with durvalumab is currently underway.

Further, only picomolar concentrations of tivozanib are required to target these VEGF receptors and prevent phosphorylation; this potency prevents the debilitating side effects that occur with treatments whose mechanisms of action involve broad-spectrum tyrosine kinase inhibition. This review summarizes the growing body of evidence supporting tivozanib's efficacy and safety in the treatment of advanced renal cell carcinoma.

A recent ph3 study combining bevacizumab (VEGF-A Mab) with a PDL1 inhibitor have shown promising improvements in OS demonstrating that a combination of VEGF and PDL1 inhibition can improve patient outcomes over single agent treatment. Phase 1 safety and efficacy findings for this novel combination will be reported at the meeting. Research Funding: AVEO Oncology

Oral plasma pharmacokinetics of tivozanib was not significantly altered in these mouse strains, nor in Cyp3a knockout and CYP3A4-humanized mice. The modest effect of ABC transporters on tivozanib brain accumulation, if also true in humans, might mean that this drug is not strongly limited in its therapeutic efficacy against malignant lesions situated partly or completely behind the blood-brain barrier.