P1/2, N=46, Terminated, Henan Cancer Hospital | Trial completion date: Jan 2026 --> Jul 2024 | Active, not recruiting --> Terminated; Investigators' decision

P2, N=130, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Sep 2024

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

P2, N=0, Withdrawn, Jiangsu Province Nanjing Brain Hospital | N=28 --> 0 | Recruiting --> Withdrawn

P2, N=130, Not yet recruiting, Fudan University

P1, N=32, Active, not recruiting, Kazia Therapeutics Limited | Recruiting --> Active, not recruiting | N=60 --> 32

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.

In the current research, we verified that anlotinib, a tyrosine kinase inhibitor with anti-lymphangiogenesis activity, and SAR131675, a selective VEGFR-3 inhibitor, effectively decreased the density of tumor lymphatic vessels in mouse cancer models, further enhancing drug accumulation in tumor tissue. Meanwhile, this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses. Our work describes a new, clinically transferrable approach to augmenting intratumoral drug accumulation, which shows great potential to address the current, unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.

P2, N=40, Not yet recruiting, Harbin Medical University

P3, N=424, Recruiting, Fudan University | Not yet recruiting --> Recruiting

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

P3, N=185, Terminated, Jiangsu HengRui Medicine Co., Ltd. | N=304 --> 185 | Recruiting --> Terminated; R&D strategy adjustment

P2, N=150, Recruiting, Kyowa Kirin, Inc. | Not yet recruiting --> Recruiting

P2, N=180, Recruiting, Kyowa Kirin, Inc. | Not yet recruiting --> Recruiting

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

P2, N=28, Recruiting, Qian Chu

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

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

P2, N=28, Recruiting, Qian Chu | Trial primary completion date: Jun 2023 --> Dec 2023

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

P2, N=180, Not yet recruiting, Kyowa Kirin, Inc.

P2, N=150, Not yet recruiting, Kyowa Kirin, Inc.

P2, N=233, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed

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.

P3, N=424, Not yet recruiting, Fudan University

Our results reveal an anticancer activity of SAR131675 on the growth and migration of ovarian cancer cells, which may be through inhibiting VEGFR-3/ERK1/2/AKT pathway. SAR131675 may serve as an effective targeted drug for ovarian cancer.

Dual FGFR and VEGFR inhibition inhibits lymphangiogenesis through suppression of c-MYC-dependent and HIF-1α-mediated HK2 expression, respectively. HK2 downregulation decreased glycolytic activity and further attenuated PD-L1 expression. Our findings suggest that dual FGFR and VEGFR blockade is an effective novel combination strategy to inhibit lymphangiogenesis and improve immunocompetence in iCCA.

P1, N=3, Terminated, Jiangsu HengRui Medicine Co., Ltd. | N=76 --> 3 | Trial completion date: Oct 2023 --> Jun 2023 | Recruiting --> Terminated; Sponsor R & D Strategy Adjustment

This enables us to select indications that might benefit from EVT801 as a monotherapy (e.g., clear cell renal cell carcinoma and soft tissue sarcomas) or in combination with standard of care. Accordingly, VEGFR-3 expression is retrospectively quantified during the EVT801 phase 1 clinical trial and may be used to stratify patients in the future.

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.

P1, N=70, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed

P2, N=0, Withdrawn, Jiangsu HengRui Medicine Co., Ltd. | N=168 --> 0 | Not yet recruiting --> Withdrawn

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.