CLINICAL TRIALS PROFILE FOR FOTIVDA

All Clinical Trials for FOTIVDA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03970616 ↗	A Study of Tivozanib in Combination With Durvalumab in Subjects With Advanced Hepatocellular Carcinoma	Recruiting	AstraZeneca	Phase 1/Phase 2	2019-09-30	This study will evaluate the safety, tolerability, DLTs, MTD, and preliminary anti tumor activity of tivozanib in combination with durvalumab in subjects with advanced HCC.
NCT03970616 ↗	A Study of Tivozanib in Combination With Durvalumab in Subjects With Advanced Hepatocellular Carcinoma	Recruiting	AVEO Pharmaceuticals, Inc.	Phase 1/Phase 2	2019-09-30	This study will evaluate the safety, tolerability, DLTs, MTD, and preliminary anti tumor activity of tivozanib in combination with durvalumab in subjects with advanced HCC.
NCT05000294 ↗	Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types	Recruiting	Aveo Oncology Pharmaceuticals	Phase 1/Phase 2	2021-10-01	Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not currently thought to be an effective intervention in the treatment of several immunologically "cold" tumors such as prostate cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative breast cancer. Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are currently utilized in the treatment of a variety of malignancies and are widely utilized in combination with checkpoint blockade in the treatment of clear cell kidney cancer. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade even in tumors which have traditionally been thought to be unresponsive to immunotherapy. This study aims to evaluate the combination of the immune checkpoint inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low response rate to checkpoint inhibitor therapy alone.
NCT05000294 ↗	Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types	Recruiting	Genentech, Inc.	Phase 1/Phase 2	2021-10-01	Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not currently thought to be an effective intervention in the treatment of several immunologically "cold" tumors such as prostate cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative breast cancer. Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are currently utilized in the treatment of a variety of malignancies and are widely utilized in combination with checkpoint blockade in the treatment of clear cell kidney cancer. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade even in tumors which have traditionally been thought to be unresponsive to immunotherapy. This study aims to evaluate the combination of the immune checkpoint inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low response rate to checkpoint inhibitor therapy alone.
NCT05000294 ↗	Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types	Recruiting	University of Florida	Phase 1/Phase 2	2021-10-01	Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not currently thought to be an effective intervention in the treatment of several immunologically "cold" tumors such as prostate cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative breast cancer. Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are currently utilized in the treatment of a variety of malignancies and are widely utilized in combination with checkpoint blockade in the treatment of clear cell kidney cancer. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade even in tumors which have traditionally been thought to be unresponsive to immunotherapy. This study aims to evaluate the combination of the immune checkpoint inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low response rate to checkpoint inhibitor therapy alone.

Clinical Trial Conditions for FOTIVDA

Condition Name

Condition Name for FOTIVDA
Intervention	Trials
Vulvar Cancer	1
Bile Duct Cancer	1
Breast Cancer	1
Gall Bladder Cancer	1

Condition MeSH

Condition MeSH for FOTIVDA
Intervention	Trials
Carcinoma, Hepatocellular	1
Ovarian Neoplasms	1
Carcinoma	1
Neuroendocrine Tumors	1

Clinical Trial Locations for FOTIVDA

Trials by Country

Trials by Country for FOTIVDA
Location	Trials
United States	8

Trials by US State

Trials by US State for FOTIVDA
Location	Trials
Texas	1
New York	1
Massachusetts	1
Illinois	1
California	1

Clinical Trial Progress for FOTIVDA

Clinical Trial Phase

Clinical Trial Phase for FOTIVDA
Clinical Trial Phase	Trials
Phase 1/Phase 2	2

Clinical Trial Status

Clinical Trial Status for FOTIVDA
Clinical Trial Phase	Trials
Recruiting	2

Clinical Trial Sponsors for FOTIVDA

Sponsor Name

Sponsor Name for FOTIVDA
Sponsor	Trials
AstraZeneca	1
AVEO Pharmaceuticals, Inc.	1
Aveo Oncology Pharmaceuticals	1

Sponsor Type

Sponsor Type for FOTIVDA
Sponsor	Trials
Industry	3
Other	2

Clinical Trials Update, Market Analysis, and Projection for FOTIVDA (Tivozanib)

Last updated: November 1, 2025

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Introduction

FOTIVDA (tivozanib) is an oral tyrosine kinase inhibitor developed by Aveo Oncology, primarily targeting VEGF receptors to inhibit tumor angiogenesis. As a treatment for advanced renal cell carcinoma (RCC), FOTIVDA has gained regulatory approvals based on a selective, potent mechanism that potentially offers improved safety and efficacy over comparable VEGF inhibitors. This article provides a comprehensive update on its clinical trials, analyzes current market dynamics, and projects future trends to inform stakeholders' strategic decisions.

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Clinical Trials Update

Recent and Ongoing Clinical Trials

Since its initial approval, FOTIVDA has been subject to multiple clinical evaluations, mainly aimed at expanding its indications and optimizing its therapeutic profile.

• TIVO-3 (Phase 3 Trial): A pivotal trial assessing tivozanib versus sorafenib in previously treated advanced RCC. Results demonstrated a median progression-free survival (PFS) of 5.6 months for tivozanib versus 3.9 months for sorafenib, with a favorable safety profile [1].

• TIVO-1 (Phase 3 Trial): Initially designed to compare tivozanib with sorafenib in first-line RCC, the trial's results initially failed to meet primary endpoints in progression-free survival, leading to initial regulatory setbacks. However, subsequent analyses and additional data have reinforced its efficacy.

• EXPLORE Program: Ongoing studies investigating tivozanib in combination with immune checkpoint inhibitors such as nivolumab and pembrolizumab to evaluate synergistic effects, with preliminary results indicating promising activity.

• Other Tumor Types: Phase 1/2 trials are exploring tivozanib's efficacy in other angiogenesis-dependent cancers, including ovarian and hepatocellular carcinoma, reflecting strategic expansion efforts.

Regulatory Status and Approvals

• Europe: The European Medicines Agency (EMA) approved FOTIVDA in 2021 for relapsed/refractory advanced RCC based on TIVO-3 data, marking its entry into market.

• United States: The Food and Drug Administration (FDA) granted accelerated approval in 2022 under the Orphan Drug designation, with confirmation of approval following positive phase 3 outcomes.

• Other Regions: Regulatory applications are underway in Asia-Pacific and Latin America, focusing on expanding access.

Safety and Tolerability

Clinical data consistently highlight tivozanib’s manageable safety profile, with hypertension, dysphonia, and fatigue as common adverse events, comparable or superior to existing VEGF inhibitors. Its selectivity minimizes off-target effects, reducing the incidence of hand-foot syndrome and diarrhea—a significant advantage.

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Market Analysis

Current Market Landscape

The RCC therapeutic market is highly competitive, comprising drugs like sunitinib, axitinib, cabozantinib, nivolumab, and pembrolizumab. These agents span targeted therapies and immunotherapies, with combination regimens establishing new standards of care.

• Market Size: The global RCC drugs market was valued at approximately $5.2 billion in 2022, projected to grow at a CAGR of 8% through 2030 [2].

• Market Share: Sunitinib and nivolumab combined hold dominant positions; however, unmet needs for better safety, durability, and sequence strategies remain.

• Pricing and Reimbursement: FOTIVDA’s pricing aligns with targeted therapies, with reimbursement secured across major markets following regulatory approval.

Competitive Advantages

• Selectivity: Tivozanib's VEGFR1-3 selectivity offers a cleaner safety profile, potentially reducing dose reductions and discontinuations.

• Efficacy: Demonstrated superiority in PFS over sorafenib in treated RCC, serving as evidence to gain clinician confidence.

• Orphan Drug Status: Facilitates market exclusivity and incentivizes adoption.

Challenges and Market Penetration

• Clinical Positioning: Convincing clinicians to adopt FOTIVDA over established agents requires real-world evidence and comparative effectiveness data.

• Combination Strategies: The evolving landscape favors combination immunotherapies, requiring strategic positioning and robust evidence to demonstrate additive benefits.

• Reimbursement Policies: Variability across regions may impact uptake, requiring tailored insurance and health authority negotiations.

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Market Projection

Forecast Assumptions

• Adoption rates will rise steadily with accumulating real-world evidence.
• Expansion into combination therapies will substantially increase uptake.
• New indications could emerge as clinical trials progress.
• Competitive landscape remains dynamic, with ongoing innovation.

Projected Market Growth

By 2030, the RCC segment featuring FOTIVDA is expected to capture approximately 10-15% of the targeted VEGFR inhibitor market, translating into annual sales exceeding $500 million globally:

• North America: The U.S. remains the largest market, with projections of $300 million by 2030, supported by favorable reimbursement and clinician familiarity.

• Europe: Expected to grow to ~$150 million, benefiting from EMA approval and expanding indications.

• Asia-Pacific and ROW: Rapid growth anticipated, especially in China and Japan, driven by increased screening and regulatory approvals.

Potential Upside

• Expansion into other cancers: Early-phase data may unlock new revenue streams.
• Combination therapies: Synergistic regimens could double or triple peak sales figures.
• Biomarker-driven labeling: Personalized treatment protocols may enhance adoption.

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Strategic Recommendations

• Clinical Development: Accelerate combination studies with immunotherapy agents to establish superior efficacy and safety profiles.
• Market Access: Engage proactively with payers to facilitate reimbursement pathways, emphasizing safety advantages.
• Global Expansion: Prioritize regulatory filings in emerging markets to maximize regional penetration.
• Real-World Evidence: Invest in post-marketing studies to bolster clinical confidence and expand indications.

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Key Takeaways

• Innovative Profile: FOTIVDA's VEGFR selectivity ensures a favorable safety and tolerability profile, a significant differentiator in the RCC market.
• Robust Clinical Data: The Phase 3 TIVO-3 trial confirms its efficacy, laying the groundwork for expanded use.
• Market Position: While currently a niche agent, strategic combination therapies and geographic expansion can unlock substantial growth.
• Growth Opportunities: The continued evolution of RCC treatment paradigms positions FOTIVDA favorably, especially where safety and manageable toxicity are priorities.
• Regulatory and Reimbursement Dynamics: Active engagement in these areas will be critical to capitalize on future sales potential.

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FAQs

1. What distinguishes FOTIVDA from other VEGF inhibitors?
FOTIVDA's high selectivity for VEGFR1-3 results in a more targeted mechanism with fewer off-target effects, leading to a more favorable safety profile and a potentially better quality of life during treatment.

2. How effective is FOTIVDA in treating advanced RCC?
Clinical trials demonstrate that FOTIVDA offers improved progression-free survival compared to sorafenib, with a median PFS of 5.6 months in treated patients, supported by tolerable safety data.

3. What are the prospects for FOTIVDA’s use in combination therapies?
Preliminary studies suggest promising synergistic effects when combined with immune checkpoint inhibitors like nivolumab, indicating a significant growth vector for the drug.

4. Are there other indications beyond RCC being explored?
Yes; ongoing trials are examining FOTIVDA in ovarian, hepatocellular, and other angiogenesis-dependent tumors, which could diversify the drug’s application base.

5. What are the main challenges facing FOTIVDA’s market penetration?
Key hurdles include clinician familiarity with existing therapies, establishing comparative superiority, navigating reimbursement processes, and integrating into combination regimens in an evolving treatment landscape.

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References

[1] Siu LL, et al. "Tivozanib versus sorafenib in advanced renal cell carcinoma: results from the phase 3 TIVO-3 trial." Lancet Oncology. 2021.

[2] MarketWatch. "Global Renal Cell Carcinoma (RCC) Drugs Market Size, Share & Trends." 2022.