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DRUG CLASS:

VEGFR-3 inhibitor

18d
New P3 trial
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Keytruda (pembrolizumab) • Fotivda (tivozanib)
22d
TiNivo-2: Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma (clinicaltrials.gov)
P3, N=343, Active, not recruiting, AVEO Pharmaceuticals, Inc. | Trial completion date: Aug 2025 --> Jul 2026 | Trial primary completion date: Aug 2024 --> Apr 2024
Trial completion date • Trial primary completion date • Combination therapy • Checkpoint inhibition
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Opdivo (nivolumab) • Fotivda (tivozanib)
26d
Resveratrol enhances sensitivity of renal cell carcinoma to tivozanib: An in-vitro study. (PubMed, Tissue Cell)
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.
Preclinical • Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • CDH1 (Cadherin 1) • BAX (BCL2-associated X protein) • VEGFC (Vascular Endothelial Growth Factor C) • KLK3 (Kallikrein-related peptidase 3)
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CDH1 expression • HIF1A expression
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Fotivda (tivozanib)
2ms
IMMCO-1: Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types (clinicaltrials.gov)
P1/2, N=29, Recruiting, University of Florida | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025
Trial completion date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
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HER-2 positive • HER-2 negative • HER-2 negative + HR negative • HER-2 positive + HR negative • HR negative + HER-2 positive
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Tecentriq (atezolizumab) • Fotivda (tivozanib)
3ms
An Exploratory Clinical Study of Adebelimumab in Combination With Famitinib and Chemotherapy in Patients With NSCLC (clinicaltrials.gov)
P2, N=0, Withdrawn, Jiangsu Province Nanjing Brain Hospital | N=28 --> 0 | Recruiting --> Withdrawn
Enrollment change • Trial withdrawal • Combination therapy
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5-fluorouracil • irinotecan • leucovorin calcium • famitinib (SHR 1020)
4ms
New P2 trial • IO biomarker
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BRCA (Breast cancer early onset)
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AiRuiKa (camrelizumab) • famitinib (SHR 1020) • M9466
5ms
Safety, Tolerability, and Pharmacokinetics of EVT801 in Patients With Advanced Solid Tumours (clinicaltrials.gov)
P1, N=32, Active, not recruiting, Kazia Therapeutics Limited | Recruiting --> Active, not recruiting | N=60 --> 32
Enrollment closed • Enrollment change • Metastases
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FLT4 (Fms-related tyrosine kinase 4)
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EVT801
7ms
Tivozanib-induced activation of the mitochondrial apoptotic pathway and suppression of epithelial-to-mesenchymal transition in oral squamous cell carcinoma. (PubMed, Korean J Physiol Pharmacol)
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.
Journal
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BCL2 (B-cell CLL/lymphoma 2) • CDH1 (Cadherin 1) • CA9 (Carbonic anhydrase 9) • CDH2 (Cadherin 2)
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Fotivda (tivozanib)
7ms
Anti-lymphangiogenesis for boosting drug accumulation in tumors. (PubMed, Signal Transduct Target Ther)
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.
Journal
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FLT4 (Fms-related tyrosine kinase 4)
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Focus V (anlotinib) • SAR131675
8ms
New P2 trial • Combination therapy
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cisplatin • carboplatin • etoposide IV • famitinib (SHR 1020) • Ariely (adebrelimab)
9ms
Enrollment open • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 expression • PGR expression
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carboplatin • AiRuiKa (camrelizumab) • albumin-bound paclitaxel • famitinib (SHR 1020)
9ms
IMMCO-1: Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types (clinicaltrials.gov)
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
Enrollment open • Trial completion date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
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HER-2 positive • HER-2 negative • HR negative + HER-2 positive
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Tecentriq (atezolizumab) • Fotivda (tivozanib)
9ms
Efficacy and Safety of Famitinib Versus Sunitinib in the Treatment of Advanced Gastrointestinal Stromal Tumour Patients After Failure of Imatinib (clinicaltrials.gov)
P3, N=185, Terminated, Jiangsu HengRui Medicine Co., Ltd. | N=304 --> 185 | Recruiting --> Terminated; R&D strategy adjustment
Enrollment change • Trial termination • Stroma • Metastases
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PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
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imatinib • sunitinib • famitinib (SHR 1020)
9ms
Phase 2 Study to Assess the Efficacy & Safety of KHK4951 in Patients With Diabetic Macular Edema (clinicaltrials.gov)
P2, N=150, Recruiting, Kyowa Kirin, Inc. | Not yet recruiting --> Recruiting
Enrollment open
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Eylea (aflibercept intravitreal)
9ms
Enrollment open
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Eylea (aflibercept intravitreal)
10ms
Phase 2 Study of Combination Tivozanib and Nivolumab in Advanced Non-Clear Cell Renal Cell Carcinoma (clinicaltrials.gov)
P2, N=48, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting
Enrollment open • Metastases
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Opdivo (nivolumab) • Fotivda (tivozanib)
11ms
Trial completion date • Metastases
|
AiRuiKa (camrelizumab) • famitinib (SHR 1020)
11ms
Trial completion date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
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HER-2 positive • HER-2 negative • HR negative + HER-2 positive
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Tecentriq (atezolizumab) • Fotivda (tivozanib)
12ms
Enrollment change
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Opdivo (nivolumab) • Fotivda (tivozanib)
12ms
Trial primary completion date • Metastases
|
AiRuiKa (camrelizumab) • famitinib (SHR 1020)
1year
Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers (clinicaltrials.gov)
P1/2, N=24, Recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2
Phase classification
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Fotivda (tivozanib)
1year
New P2 trial
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Eylea (aflibercept intravitreal)
1year
New P2 trial
|
Eylea (aflibercept intravitreal)
1year
Study to Evaluate the Efficacy and Safety of Camrelizumab and Famitinib in Patients With Advanced Solid Tumor (clinicaltrials.gov)
P2, N=233, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed
Trial completion • Metastases
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PD-L1 (Programmed death ligand 1)
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AiRuiKa (camrelizumab) • famitinib (SHR 1020)
1year
IMMCO-1: Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types (clinicaltrials.gov)
P1/2, N=29, Recruiting, University of Florida | Trial completion date: Dec 2024 --> Jun 2024
Trial completion date
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HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
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HER-2 positive • HER-2 negative • HR negative + HER-2 positive
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Tecentriq (atezolizumab) • Fotivda (tivozanib)
1year
Comparative docking analysis of tyrosine kinase inhibitors with HER2 and HER4 receptors. (PubMed, Bioinformation)
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.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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HER-2 overexpression
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Xalkori (crizotinib) • erlotinib • gefitinib • lapatinib • Zykadia (ceritinib) • Fotivda (tivozanib)
1year
New P3 trial • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 expression • PGR expression
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carboplatin • AiRuiKa (camrelizumab) • albumin-bound paclitaxel • famitinib (SHR 1020)
1year
SAR131675 exhibits anticancer activity on human ovarian cancer cells through inhibition of VEGFR-3/ERK1/2/AKT signaling pathway. (PubMed, Cell Signal)
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.
Journal
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FLT4 (Fms-related tyrosine kinase 4) • VEGFC (Vascular Endothelial Growth Factor C)
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SAR131675
1year
Dual FGFR and VEGFR inhibition synergistically restrain hexokinase 2-dependent lymphangiogenesis and immune escape in intrahepatic cholangiocarcinoma. (PubMed, J Gastroenterol)
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.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • FLT4 (Fms-related tyrosine kinase 4) • VEGFC (Vascular Endothelial Growth Factor C) • HK2 (Hexokinase 2)
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PD-L1 expression • HIF1A expression
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Truseltiq (infigratinib) • SAR131675
over1year
A Study of SHR6390 Combined With Famitinib in the Treatment of ER + / HER2- Advanced Breast Cancer (clinicaltrials.gov)
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
Enrollment change • Trial completion date • Trial termination • Combination therapy • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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HER-2 negative
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AiRuiKang (dalpiciclib) • famitinib (SHR 1020)
over1year
VEGFR-3 expression profiling by histology and mRNA signature to classify patient population for the selective VEGFR-3 inhibitor EVT801 (ESMO 2023)
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.
Clinical
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CD34 (CD34 molecule) • FLT4 (Fms-related tyrosine kinase 4)
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EVT801
over1year
Clinical Outcomes of Tivozanib Monotherapy as First-Line Treatment for Metastatic Renal Cell Carcinoma: A Multicentric UK Real-World Analysis. (PubMed, Target Oncol)
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.
Clinical data • Retrospective data • Journal • Real-world evidence • Real-world • Metastases
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Fotivda (tivozanib)
over1year
DEDUCTIVE: A Study of Tivozanib in Combination With Durvalumab in Subjects With Advanced Hepatocellular Carcinoma (clinicaltrials.gov)
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.
Enrollment change • Trial termination • Combination therapy • Metastases
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Imfinzi (durvalumab) • Fotivda (tivozanib)
over1year
TiNivo-2: Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma (clinicaltrials.gov)
P3, N=326, Active, not recruiting, AVEO Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy • Checkpoint inhibition
|
Opdivo (nivolumab) • Fotivda (tivozanib)
over1year
Activity of Tivozanib in Non-clear Cell Renal Cell Carcinoma: Subgroup Analysis From a Phase II Randomized Discontinuation Trial. (PubMed, Oncologist)
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.
P2 data • Journal
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Fotivda (tivozanib)
over1year
Pharmacokinetics Study of Famitinib Malate Capsules in Healthy Subjects (clinicaltrials.gov)
P1, N=70, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed
Trial completion
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famitinib (SHR 1020)
over1year
A Trial of SHR-1701 With or Without Famitinib in Patients With Advanced or Metastatic NSCLC (clinicaltrials.gov)
P2, N=0, Withdrawn, Jiangsu HengRui Medicine Co., Ltd. | N=168 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal • Metastases
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retlirafusp alfa (SHR-1701) • famitinib (SHR 1020)
over1year
Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model. (PubMed, Pharmaceuticals (Basel))
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.
Preclinical • Journal
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Fotivda (tivozanib)
over1year
HPLC methods for studying pharmacokinetics of tivozanib and in vitro metabolic interaction with dexamethasone in rat. (PubMed, J Pharm Biomed Anal)
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.
PK/PD data • Preclinical • Journal
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dexamethasone • Fotivda (tivozanib)
over1year
Bioequivalence Study of Famitinib Malate in Healthy Volunteers Under Fasting Condition (clinicaltrials.gov)
P1, N=28, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed
Trial completion
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famitinib (SHR 1020)
over1year
GeneCentric Therapeutics Initiates the Alamance Study – A Real-World Investigation of Bladder Cancer Patients Treated with FGFR Inhibitors and Other Standards of Care (Businesswire)
"GeneCentric Therapeutics...announced today the initiation of its Alamance study, a multi-center bladder cancer study conducted in collaboration with investigators at Memorial Sloan Kettering Cancer Center and the University of Wisconsin – Madison Carbone Cancer Center....In this prospectively designed real-world evidence study, clinical response data and existing tumor samples are being collected from a multi-center cohort of approximately 250 patients with locally advanced or metastatic urothelial (bladder) cancer treated with FGFR-targeted therapy (e.g., erdafitinib) or other standards of care (e.g., anti-PD-(L)1 or platinum-based chemotherapy)."
New trial
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FGFR-PRS test
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Balversa (erdafitinib)