^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
DRUG CLASS:

VEGFR-1 inhibitor

14d
Denfivontinib activates effector T-cells through NLRP3-inflammasome, yielding potent anticancer effects by combination with pembrolizumab. (PubMed, Mol Cancer Ther)
To demonstrate the extent to which our findings reflect clinical results, we analyzed bulk-RNA sequencing data from 21 NSCLC patients undergoing anti-PD-1 immunotherapy. The NLRP3 inflammasome score influenced enhanced immune responses in patient data undergoing anti-PD-1 immunotherapy, suggesting a role for NLRP3 inflammasome in activating immune responses during treatment.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • NLRP3 (NLR Family Pyrin Domain Containing 3)
|
IFNG expression
|
Keytruda (pembrolizumab) • denfivontinib (SKI-G-801)
2ms
New P3 trial
|
Keytruda (pembrolizumab) • Fotivda (tivozanib)
2ms
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
|
Opdivo (nivolumab) • Fotivda (tivozanib)
2ms
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
|
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)
|
CDH1 expression • HIF1A expression
|
Fotivda (tivozanib)
3ms
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
|
HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
|
HER-2 positive • HER-2 negative • HER-2 negative + HR negative • HER-2 positive + HR negative • HR negative + HER-2 positive
|
Tecentriq (atezolizumab) • Fotivda (tivozanib)
6ms
Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer. (PubMed, Sci Rep)
The results of Molecular Docking indicated that PubChem IDs-71465,645 and 11152946 exhibited strong affinity, designating them as the most efficient molecules. To further investigate their potential, a Molecular Dynamics Simulation was performed to assess conformational stability, and a pharmacophore analysis was also conducted for indoctrinating interactions.
Journal
|
KDR (Kinase insert domain receptor) • FLT1 (Fms-related tyrosine kinase 1) • FLT4 (Fms-related tyrosine kinase 4) • VEGFD (Vascular Endothelial Growth Factor D) • VEGFB (Vascular Endothelial Growth Factor B) • VEGFC (Vascular Endothelial Growth Factor C)
8ms
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
|
BCL2 (B-cell CLL/lymphoma 2) • CDH1 (Cadherin 1) • CA9 (Carbonic anhydrase 9) • CDH2 (Cadherin 2)
|
Fotivda (tivozanib)
8ms
The eEF1A Protein in Cancer: Clinical Significance, Oncogenic Mechanisms, and Targeted Therapeutic Strategies. (PubMed, Pharmacol Res)
Among them, plitidepsin was approved for the treatment of multiple myeloma whereas metarrestin was currently under clinical development. Despite significant achievements in these two interrelated fields, hitherto there lacks a systematic examination of the eEF1A protein in the context of cancer research. Therefore, the present work aims to delineate its clinical implications, molecular oncogenic mechanisms, and targeted therapeutic strategies as reflected in the ever expanding body of literature, so as to deepen mechanistic understanding of eEF1A-involved tumorigenesis and inspire the development of eEF1A-targeted chemotherapeutics and biologics.
Review • Journal
|
EEF1A1 (Eukaryotic Translation Elongation Factor 1 Alpha 1)
|
Aplidin (plitidepsin)
8ms
Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition. (PubMed, Mar Drugs)
However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.
Review • Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
Aplidin (plitidepsin) • echinomycin
8ms
NEREIDA: Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care (clinicaltrials.gov)
P2, N=37, Terminated, PharmaMar | N=150 --> 37 | Active, not recruiting --> Terminated; Significant difficulties in the recruitment of patients
Enrollment change • Trial termination
|
CD4 (CD4 Molecule)
|
Aplidin (plitidepsin)
8ms
Recent advances in tyrosine kinase inhibitors VEGFR 1-3 for the treatment of advanced metastatic melanoma. (PubMed, Expert Opin Pharmacother)
On the contrary, some patients with mucosal, acral or KIT-mutant melanoma may benefit from TKI-based therapies. Further studies focused on biomarker discovery and randomized trials are necessary to better understand the role of VEGFR1-3 as a therapeutic target in melanoma.
Review • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • FLT1 (Fms-related tyrosine kinase 1)
|
KIT mutation
|
Lenvima (lenvatinib) • AiTan (rivoceranib) • Inlyta (axitinib)
9ms
NEREIDA: Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care (clinicaltrials.gov)
P2, N=150, Active, not recruiting, PharmaMar | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Apr 2024 | Trial primary completion date: Jun 2025 --> Mar 2024
Enrollment closed • Trial completion date • Trial primary completion date
|
CD4 (CD4 Molecule)
|
Aplidin (plitidepsin)
10ms
Enrollment closed • Metastases
|
denfivontinib (SKI-G-801)
10ms
Trial completion • Enrollment change
|
denfivontinib (SKI-G-801)
10ms
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
|
HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
|
HER-2 positive • HER-2 negative • HR negative + HER-2 positive
|
Tecentriq (atezolizumab) • Fotivda (tivozanib)
10ms
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
|
Eylea (aflibercept intravitreal)
10ms
Enrollment open
|
Eylea (aflibercept intravitreal)
11ms
New P2 trial • Metastases
11ms
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
|
Opdivo (nivolumab) • Fotivda (tivozanib)
12ms
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
|
HER-2 positive • HER-2 negative • HR negative + HER-2 positive
|
Tecentriq (atezolizumab) • Fotivda (tivozanib)
1year
Trial completion date • Trial primary completion date
|
CD4 (CD4 Molecule)
|
Aplidin (plitidepsin)
1year
Enrollment change
|
Opdivo (nivolumab) • Fotivda (tivozanib)
1year
Multicenter Trial of ESK981 in Patients With Select Solid Tumors (clinicaltrials.gov)
P2, N=66, Not yet recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Sep 2028 --> Jan 2029 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Aug 2026 --> Jan 2027
Trial completion date • Trial initiation date • Trial primary completion date
|
SYP (Synaptophysin) • CHGA (Chromogranin A)
|
ESK981
1year
EEF1A2 promotes HIF1A mediated breast cancer angiogenesis in normoxia and participates in a positive feedback loop with HIF1A in hypoxia. (PubMed, Br J Cancer)
EEF1A2 exhibits angiogenic potential in both normoxic and hypoxic conditions, underscoring its dual role in promoting EMT and angiogenesis, rendering it a promising target for cancer therapy.
Journal
|
PGR (Progesterone receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
ER positive + PGR positive • PGR positive • MYC expression • HIF1A expression
|
Aplidin (plitidepsin)
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
|
Fotivda (tivozanib)
1year
New P2 trial
|
Eylea (aflibercept intravitreal)
1year
New P2 trial
|
Eylea (aflibercept intravitreal)
1year
NEREIDA: Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care (clinicaltrials.gov)
P2, N=150, Recruiting, PharmaMar | Trial completion date: Aug 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jun 2025
Trial completion date • Trial primary completion date
|
CD4 (CD4 Molecule)
|
Aplidin (plitidepsin)
over1year
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
|
HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
|
HER-2 positive • HER-2 negative • HR negative + HER-2 positive
|
Tecentriq (atezolizumab) • Fotivda (tivozanib)
over1year
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
|
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)
|
HER-2 overexpression
|
Xalkori (crizotinib) • erlotinib • gefitinib • lapatinib • Zykadia (ceritinib) • Fotivda (tivozanib)
over1year
Compassionate Use of Plitidepsin in Patients With Non‑Hodgkin Lymphoma (NHL) and SARS‑CoV‑2 Infection (SOHO 2023)
Sixty percent (3/5) had received 6 cycles of obitunuzumab and bendamustine (the last dose in patients 1 and 2 were administered 2 years prior to admission). Patients 2 and 5 had received rituximab maintenance, the last dose being administered in both < 2 months prior to admission for SARS-CoV-2. Patient 3 had received 6 cycles of obinutuzumab-COMP and maintenance with obinutuzumab, with the last dose administered 9 months before admission for SARS-COV-2... Plitidepsin shows a good safety profile in patients with NHL and SARS-CoV-2 infection. Four of the 5 patients presented resolution of SARS-CoV-2 infection. Prospective studies are needed to confirm the effectiveness of plitidepsin as a treatment for SARS-CoV-2 infection in patients with NHL who have received immunochemotherapy.
Clinical
|
EEF1A1 (Eukaryotic Translation Elongation Factor 1 Alpha 1)
|
Rituxan (rituximab) • Gazyva (obinutuzumab) • bendamustine • Aplidin (plitidepsin)
over1year
Multicenter Trial of ESK981 in Patients With Select Solid Tumors (clinicaltrials.gov)
P2, N=66, Not yet recruiting, University of Michigan Rogel Cancer Center
New P2 trial
|
SYP (Synaptophysin) • CHGA (Chromogranin A)
|
ESK981
over1year
Outcomes and clinical characteristics of the compassionate use of plitidepsin for immunocompromised adult patients with COVID-19. (PubMed, Int J Infect Dis)
These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.
Journal
|
Aplidin (plitidepsin)
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
|
Fotivda (tivozanib)
over1year
ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer (clinicaltrials.gov)
P2, N=13, Completed, Barbara Ann Karmanos Cancer Institute | Active, not recruiting --> Completed | N=27 --> 13
Trial completion • Enrollment change • Metastases
|
ESK981
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
|
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
A dose escalation/expansion study evaluating dose, safety, and efficacy of the novel tyrosine kinase inhibitor surufatinib, which inhibits VEGFR 1, 2, & 3, FGFR 1, and CSF1R, in US patients with neuroendocrine tumors. (PubMed, Invest New Drugs)
Pharmacokinetics, safety, and antitumor efficacy of 300 mg QD oral surufatinib in US patients with pNETs and epNETs are consistent with previously reported studies in China and may support applicability of earlier surufatinib studies in US patients. Clinical trial registration: Clinicaltrials.gov NCT02549937.
Journal
|
FGFR1 (Fibroblast growth factor receptor 1) • FLT1 (Fms-related tyrosine kinase 1) • CSF1R (Colony stimulating factor 1 receptor)
|
Sulanda (surufatinib)
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
|
Fotivda (tivozanib)
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
|
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
|
dexamethasone • Fotivda (tivozanib)