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

Patient-reported outcomes (PROs) for tivozanib (TIVO) + nivolumab (NIVO) vs TIVO monotherapy in patients with renal cell carcinoma (RCC) following an immune checkpoint inhibitor (ICI): Results of the phase 3 TiNivo-2 study. (ASCO-GU 2025) - P3 | "There were no differences in the PRO outcomes between the combination therapy and monotherapy arms or between the 2 different TIVO doses. PRO data suggested that TIVO maintained the FKSI-DRS and EORTC QLQ-C30 mean scores from BL to week 24. In the TIVO arm, the proportion of patients who had improvement in FKSI-DRS and EORTC QLQ-C30 scores was numerically better in patients receiving 2L vs 3L treatment, while the portion of patients with a deterioration was smaller in the 2L than in the 3L."

Checkpoint inhibition • Clinical • Monotherapy • P3 data • Patient reported outcomes • Genito-urinary Cancer • Oncology • Solid Tumor

Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study. (PubMed, Lancet) - P3 | "These data further support that ICI rechallenge should be discouraged in patients with advanced renal cell carcinoma. Furthermore, these data suggest that tivozanib monotherapy has efficacy in the post-ICI setting."

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

Tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) following 1 or 2 prior therapies including an immune checkpoint inhibitor (ICI): Results of the phase III TiNivo-2 study (ESMO 2024) - P3 | "ICI combination rechallenge did not improve clinical outcomes, suggesting the avoidance of sequential ICI in advanced RCC outside of clinical trials. These results support tivozanib monotherapy at 1.34 mg daily as 2nd-line therapy for pts following progression on previous ICI combination therapy."

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

Real-world efficacy and safety of tivozanib in metastatic renal cell carcinoma in a diverse cohort: A multicenter study from the City of Hope enterprise. (ASCO-GU 2026) - "The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Metastases • Real-world • Real-world effectiveness • Real-world evidence • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Drug-Drug Interactions as a Challenge in the Monotherapy of Advanced or Metastatic Clear-Cell Renal Cell Carcinoma with VEGFR-Associated Tyrosine Kinase Inhibitors (PubMed, Aktuelle Urol) - "This article provides practical recommendations for side-effect and medication management, with a particular focus on pharmacokinetic and pharmacodynamic drug-drug interactions. Tivozanib, a potent VEGFR-TKI, is well-suited and recommended as a first-line treatment option for mRCC due to its comparatively favorable safety profile and beneficial interaction potential."

Journal • Monotherapy • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Updated overall survival in patients with prior checkpoint inhibitor therapy in the phase III TIVO-3 study. (PubMed, Oncologist) - "In this long-term post-hoc update of the TIVO-3 trial, we show that in CPI-resistant mRCC, the PFS benefit of tivozanib over sorafenib is accompanied with improved OS data, although not statistically significant, and durable responses."

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

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

Short term intensified pembrolizumab and tivozanib for high-risk renal cell carcinoma: STRIKE! (Alliance A032201). (ASCO-GU 2026) - P3 | "Clinical Trial Registry Number: NCT06661720. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

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

SOGUG-TIVOREAL: Real World Evidence of Tivozanib as First-line Treatment for Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P=N/A | N=200 | Completed | Sponsor: Spanish Oncology Genito-Urinary Group

HEOR • New trial • Real-world evidence • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Activity of tivozanib in non-clear cell renal cell carcinoma (nccRCC): Subgroup analysis from a phase 2 randomized discontinuation trial. (ASCO 2022) - P2 | "Tivozanib demonstrated activity and a favorable safety profile in patients with nccRCC. This data adds to the body of evidence supporting VEGFR TKI use in advanced RCC including in non-clear cell histologies."

Clinical • P2 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Tivozanib in Patients with Advanced Renal Cell Carcinoma Previously Treated With Axitinib: Subgroup Analysis from TIVO-3. (PubMed, Oncologist) - "Tivozanib is active in the treatment of patients with mRCC who have progressed on prior therapies, including axitinib."

Journal • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Temporal Characteristics of Adverse Events of Tivozanib and Sorafenib in Previously Treated Kidney Cancer. (PubMed, Clin Genitourin Cancer) - "Tivozanib was associated with less TRAEs, fewer dose modifications, a longer time to onset and a shorter duration of TRAEs compared to sorafenib."

Adverse events • Journal • Genito-urinary Cancer • Immunology • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Activity of Tivozanib in Non-clear Cell Renal Cell Carcinoma: Subgroup Analysis From a Phase II Randomized Discontinuation Trial. (PubMed, Oncologist) - P2 | "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."

Journal • P2 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Mechanistic insights into Gwt1-substrate interactions and antifungal drug discovery via molecular dynamics and virtual screening. (PubMed, J Biomol Struct Dyn) - "Leveraging these structural insights, we performed virtual screening targeting the hydrophobic pocket formed by Tyr129, Tyr400, Phe404, and Tyr408, which identified two approved drugs, tivozanib and rosiglitazone, as potential Gwt1 inhibitors. Experimental validation confirmed their antifungal activities against pathogenic fungi, including Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus. This work provides dynamic mechanistic insights into Gwt1 function and offers a rational strategy for repurposing existing drugs as antifungals targeting the GPI pathway."

Journal

IMMCO-1: Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types (clinicaltrials.gov) - P1/2 | N=29 | Suspended | Sponsor: University of Florida | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Platinum resistant • Trial completion date • Trial primary completion date • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Estrogen Receptor Positive Breast Cancer • Gallbladder Cancer • Gynaecological Neuroendocrine Tumor • Gynecologic Cancers • HER2 Positive Breast Cancer • 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

First-Line Treatment with Tivozanib for Metastatic Renal Cell Carcinoma in Real-World Settings Across Germany: Results of the Prospective, Non-Interventional, Post-Approval Study T-Rex. (PubMed, Cancers (Basel)) - "These data demonstrate that first-line treatment with tivozanib was associated with clinical activity, favorable tolerability, and stable QoL in patients with mRCC treated in everyday clinical practice across Germany, including those with advanced age."

Journal • Real-world evidence • Cardiovascular • Dermatology • Genito-urinary Cancer • Hypertension • Hypotension • Oncology • Renal Cell Carcinoma • Solid Tumor

Positioning Tivozanib in Today’s RCC Treatment Landscape (YouTube) - "Medical oncologists review standard-of-care treatments and therapy goals for patients with advanced RCC after first-line TKI or immunotherapy regimens."

Video • Renal Cell Carcinoma

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."

Audio

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