Fotivda (tivozanib) / Kyowa Kirin, Jazz, LG Chem, Recordati - LARVOL DELTA

Sitagliptin does not interfere with VEGF-A signaling in retinal endothelial cells in vitro. (PubMed, Exp Clin Endocrinol Diabetes) - "The VEGF-A165-induced declines of the cell index and TJ-protein claudin-1 were prevented by tivozanib, and this process was not modulated by sitagliptin.The underlying mechanisms of barrier dysfunctions caused by sitagliptin or VEGF-A are different and independent. Most importantly, the DPP-4 inhibitor does not interfere with blocking VEGF signaling to correct VEGF-A-dependent barrier dysfunction."

Journal • Preclinical • Diabetes • Diabetic Macular Edema • Metabolic Disorders • Ophthalmology • Type 2 Diabetes Mellitus • CLDN1 • CLDN5

Identification and Structural Characterization of Degradation Products of Tivozanib Using LC-Q-TOF-MS/MS and NMR: An In Silico Approach for Degradation and Toxicity Prediction. (PubMed, Rapid Commun Mass Spectrom) - "Forced degradation studies were conducted in accordance with ICH Q1A (R2) and Q1B guidelines. Totally, seven DPs were observed in various stress conditions. DP-IV, a structural isomer of TVZ, was detected in basic hydrolytic conditions. The developed RP-HPLC method was validated following the ICH Q2(R1). This study helps in the stability testing and routine quality control analysis during the formulation development of TVZ."

Journal

Tivozanib-Induced Immune Thrombocytopenia in Metastatic Renal Cell Carcinoma: A Case Report and Review (ASH 2024) - "This case report represents one of the initial documented cases detailing the observation of severe Drug-induced immune thrombocytopenia after the initiation of tivozanib treatment in a patient.Case PresentationA 52-year-old male with a history of diabetes mellitus, recent pulmonary embolism on apixaban, and metastatic RCC presented with worsening shortness of breath and hemoptysis three months after initiating tivozanib treatment...Therefore, patient was started on dexamethasone, and intravenous immunoglobulin (IVIG)...However, when tivozanib is used in combination therapies, such as with everolimus or temsirolimus, the incidence of severe thrombocytopenia appears to increase...Testing for drug-specific antiplatelet antibodies can confirm the diagnosis, although this testing may not be widely available.ConclusionIn conclusion, in this case report, we described an incident of tivozanib-induced ITP which suggests that future monitoring of cancer patient placed on TKIs may..."

Case report • Clinical • Metastases • Review • Cardiovascular • Diabetes • Genito-urinary Cancer • Hematological Disorders • Immune Thrombocytopenic Purpura • Metabolic Disorders • Oncology • Pulmonary Embolism • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor • Thrombocytopenia • Thrombocytopenic Purpura • FLT1

2-Chloro-4-hy-droxy-anilinium chloride. (PubMed, IUCrdata) - "The NH3 + substituent donates three inter-molecular hydrogen bonds to chloride ions having N⋯Cl distances in the range 3.1514 (6)-3.3019 (2) Å, and the OH group donates an inter-molecular hydrogen bond to chloride with O⋯Cl distance 3.0671 (6) Å. The chloro substituent and OH group do not accept hydrogen bonds from NH or OH."

Journal • Oncology

Lymph Node Transcriptomics in Idiopathic Multicentric Castleman Disease (iMCD) Identifies Pathogenic Mechanisms and Biomarkers Including Increased Clusterin Expression (ASH 2024) - "A VEGF inhibitor, Tivozanib, and an NF-kB inhibitor, Parthenolide, were two of the top therapies predicted to reverse the iMCD-TAFRO gene signature, neither of which have been reported in the literature for use in iMCD-TAFRO...Clusterin may differentiate iMCD from other inflammatory and neoplastic conditions, but further work needs to be done to confirm this finding. We also used in-silico methods to identify increased numbers of plasma cells and monocytes in iMCD LN tissue, and identified VEGF and TNF inhibition as potential therapeutic invterventions in iMCD."

Biomarker • Clinical • Diffuse Large B Cell Lymphoma • Hematological Disorders • Inflammatory Arthritis • Nephrology • Oncology • Rare Diseases • Renal Disease • Thrombocytopenia • Thrombocytosis • CLU • IL6 • SPP1 • XBP1

Buccodental Toxicities Induced by Tyrosine Kinase Inhibitors in Patients Diagnosed with Renal Cell Carcinoma-A Literature Review. (PubMed, Dent J (Basel)) - "The following keywords were used: Axitinib, Cabozantinib, Lenvatinib, Pazopanib, Sorafenib, Sunitinib, and Tivozanib. RCC therapies have been proven to frequently induce oral symptoms and pathologies such as stomatitis, dysgeusia, xerostomia, osteonecrosis of the jaws, oral dysesthesia, geographic tongue, and dental and periodontal damage. The aim of this review is to emphasize the mechanisms of these common drug-induced buccodental toxicities associated with TKI therapies in RCC and to draft a general clinical management of these adverse events, in order to improve patients' quality of life and treatment adherence."

Journal • Review • Dental Disorders • Genito-urinary Cancer • Kidney Cancer • Mucositis • Oncology • Oral Cancer • Renal Cell Carcinoma • Solid Tumor • Stomatitis • Xerostomia

Insurance and Tolerability Factors Considered in Recurrent RCC Treatment (Targeted Oncology) - "During a live event, Nizar M. Tannir, MD and participants discussed their takeaways from trial data on recurrent RCC treatment and their personal experiences."

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RP2 and Tivozanib for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Association of HTR1F with Prognosis, Tumor Immune Microenvironment, and Drug Sensitivity in Cancer: A Multi-Omics Perspective. (PubMed, Biomedicines) - "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."

Journal • Tumor mutational burden • Immune Modulation • Immunology • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • MSI • TMB

Medication-related jaw osteonecrosis in metastatic RCC treated with VEGFR-TKIs ± IO and bone agents: A real-world analysis. (PubMed, Tumori) - "Bone-targeted therapies (BTT), denosumab (Dmab) and zoledronic acid (ZOL AC), reduce SREs but are associated with a risk of Medication-Related Osteonecrosis of the Jaw (MRONJ), especially when combined with Vascular Endothelial Growth Factor Receptor - Tyrosine Kinase Inhibitors (VEGFR-TKIs)...At ONJ diagnosis, 10/12 patients were on VEGFR-TKI, one on IO (previously on pazopanib), and one off therapy (previously on tivozanib)...This study represents one of the largest real-world cohorts assessing MRONJ incidence in mRCC patients treated with VEGFR-TKIs and IO-combo with concomitant BTT. Our findings confirm an MRONJ rate consistent with prior reports (10-17%) of patients treated with TKIs monotherapy and BTT."

Journal • Real-world evidence • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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 | Sponsor: AVEO Pharmaceuticals, Inc. | Trial completion date: Jul 2026 ➔ Dec 2025 | Trial primary completion date: Apr 2024 ➔ Sep 2025

Checkpoint inhibition • Monotherapy • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Sequencing for Metastatic Clear Cell Renal Cell Carcinoma After Prior Therapy : Episode 29: Assessing Tivozanib Efficacy in Metastatic RCC Treatment (Targeted Oncology) - "During a live event, Sumanta K. Pal, MD, discussed lenvatinib dosing and tivozanib efficacy for patients with metastatic renal cell carcinoma."

Media quote • Renal Cell Carcinoma

FAHD1-Mediated Pyruvate Metabolism in hepatocellular carcinoma: Multi-Omics and Causal Genetic Evidence. (PubMed, HGG Adv) - "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."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • ITGB2 • TGFB1

Short TeRm Intensified Pembrolizumab (KEytruda) and Tivozanib for Hogh-Risk Renal Cell Carcinoma – STRIKE! (A033201) -NCT06661720 (KCRS 2025) - P3 | "is the first trial and only trial to explore the role of adding a VEGF TKI to immunotherapy in the adjuvant setting for resected high risk ccRCC. Correlative analysis will be essential to develop-ment of biomarkers of minimal residual disease and response to therapy."

IO biomarker • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

IMMCO-1: Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: University of Florida | Trial primary completion date: Jun 2025 ➔ Dec 2025

Platinum resistant • Trial primary completion date • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gynecologic Cancers • Hormone Receptor Negative Breast Cancer • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Vulvar Cancer • CD4 • HER-2 • TMB

Overview of Tivozanib (Tivo) safety in phase 3 clinical trials in patients with metastatic renal cell carcinoma (mRCC) (KCRS 2025) - "In TiNivo-2, patients with mRCC who had previous exposure to ICI, were randomized to receive study treatment as 2L or 3L with Tivo alone at 1.34 mg, or at 0.89 mg in combination with the ICI nivolumab (nivo).[1] The addition of nivo to tivo in second line (2L) or third-line treatment (3L) did not improve outcomes, and tivo monotherapy showed activity as a 2L treatment in the post ICI setting. In TIVO-3, randomized patients had at least two previous systemic treatments and received tivo or sorafenib...Conclusions Here, results show that tivo has a manageable safety profile across phase 3 trials. The better tolerability of tivo in the TiNivo-2 study vs TIVO-3 is driven in part by more patients enrolled in the earlier lines of treatment (2L)."

Clinical • Metastases • P3 data • Cardiovascular • Genito-urinary Cancer • Hypertension • Oncology • Renal Cell Carcinoma • Solid Tumor

VHL and TP53 mutation status are not associated with response or progression-free survival in metastatic renal cell carcinoma treated with VEGF-targeted therapies (KCRS 2025) - "VEGF-targeted therapy was defined broadly to include newer generation vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs; excluding agents like sunitinib), belzutifan, and VEGF-TKI–based combinations with immunotherapy or everolimus...The most common VEGF-targeted therapies were cabozantinib, lenvatinib, axitinib, and tivozanib, frequently administered in combination with immunotherapy or everolimus...Conclusions In this ctDNA-based analysis of patients with mRCC treated with VEGF-targeted therapies, neither VHL nor TP53 mutation status was associated with meaningful differences in clinical outcomes. These findings align with prior reports and suggest that mutation status alone may not predict efficacy of VEGF-targeted regimens, even in the context of combination therapies."

IO biomarker • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • TP53 • VEGFA • VHL

Integrated Efficacy and Safety Exposure Response (ER) Analysis of Tivozanib (TIVO) for the Treatment of Renal Cell Cancer (RCC) (KCRS 2025) - "The Tivo monotherapy dose selection of 1.34 mg is important, based on the ER analysis and its safety profile. The results from the TiNivo-2 data set further confirmed that re-challenge with immunotherapy does not add benefit and optimal dosing of TKI provides the highest clinical benefit."

Clinical • Cardiovascular • Genito-urinary Cancer • Hypertension • Oncology • Renal Cell Carcinoma • Solid Tumor

Tivozanib + Enzalutamide in Adv Prostate Cancer (clinicaltrials.gov) - P2 | N=5 | Terminated | Sponsor: Massachusetts General Hospital | Active, not recruiting ➔ Terminated; Slow accrual

Trial termination • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Drug Repurposing by Virtual Screening: Identification of New Already Approved ROCK Inhibitors as Promising Drugs to Target Neurodegeneration. (PubMed, ACS Omega) - "Virtual screening led to the identification of six approved drugs as ROCK inhibitors: ruxolitinib (36), baricitinib (37), ponatinib (38), tivozanib (39), nialamide (40), and tucatinib (41). These findings not only highlight ruxolitinib (36) as a promising candidate for AD but also provide a structural basis for designing novel dual JAK-ROCK inhibitors and pave the way for further in vitro and in vivo studies. Moreover, the validated pharmacophoric map for ROCK inhibition highlights the identification of an affinity pocket that can be useful for the design of new ROCK inhibitors."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Receptor tyrosine kinase inhibitor tivozanib regulates cell state plasticity and restores MITF dependency in BRAF wild-type melanoma. (PubMed, Acta Pharmacol Sin) - "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."

Journal • Melanoma • Oncology • Ophthalmology • Solid Tumor • BRAF • MITF

Receptor tyrosine kinase inhibitor tivozanib regulates cell state plasticity and restores MITF dependency in BRAF wild-type melanoma (Nature) - "In this study, we evaluated TT-012, a recently identified MITF dimerization specific inhibitor, and surprisingly found that most BRAFWT melanoma lines were resistant to TT-012 due to low MITF transcriptional activity and reduced dependency on MITF for proliferation. High-throughput drug screen identified tivozanib, an FDA-approved drug targeting VEGFR and other receptor tyrosine kinases (RTKs), which sensitized cells to TT-012. 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."

Preclinical • Melanoma

Elevated hernia risk in renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs): A FAERS analysis. (ASCO 2025) - "Reports mentioning both RCC and TKI use were identified, specifically focusing on sunitinib, pazopanib, axitinib, cabozantinib, lenvatinib, bevacizumab, and tivozanib... Our FAERS analysis suggests a potential association between TKI use and increased hernia risk in patients with RCC. Further investigation using observational studies is crucial to confirm this association and explore underlying mechanisms. Future research should focus on validating these findings, elucidating the biological mechanisms involved, identifying risk factors, and developing clinical guidelines for hernia prevention and management in this patient population."

Clinical • Gastroenterology • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Efficacy of second line (2L) treatment with tivozanib (Tivo) as monotherapy or with nivolumab (Nivo) in patients (pts) with metastatic renal cell carcinoma (mRCC) previously treated with an immune checkpoint inhibitor (ICI) combination of ipilimumab (Ipi)/Nivo or vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI)/ICI in the phase 3 TiNivo-2 study. (ASCO 2025) - P3 | " Among the 153 eligible 2L pts, 70 (46%) previously received Ipi/Nivo and 83 (54%) previously received a VEGFR-TKI/ICI regimen (TKI/ICI): axitinib/pembrolizumab (54.2%), cabozantinib/nivolumab (25.3%), axitinib/avelumab (12.0%), and lenvatinib/pembrolizumab (8.4%)... In this TiNivo-2 subgroup analysis, Tivo monotherapy at 1.34 mg daily showed activity in pts who previously received a contemporary 1L mRCC regimen. At this dose of Tivo, substantial tumor size reduction was observed, both after Ipi/Nivo and VEGFR-TKI/ICI regimens. There appeared to be no benefit with the addition of Nivo to Tivo in this context, akin to the results of the parent trial."

Checkpoint inhibition • Clinical • Metastases • Monotherapy • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Next-gen Korean cancer fighters to showcase innovation at ASCO 2025 (Korea Biomedical Review) - "Among the companies presenting clinical results is LG Chem, which will showcase phase 3 data for Fotivda (ingredient: tivozanib), its targeted therapy for metastatic renal cell carcinoma, developed by its U.S. subsidiary AVEO...Results demonstrated favorable progression-free survival in the monotherapy arm, particularly among patients who had previously received Yervoy and Opdivo. AVEO will also present phase 3 data on ficlatuzumab, an HGF-targeting antibody in head and neck cancer, and phase 1b data for AV-380, an anti-GDF15 antibody in development for cancer cachexia."

Clinical data • Cachexia • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck