Last update 15 Nov 2024

Sorafenib Tosylate

Last update 15 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide, N-(4-Chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, SORAFENIB

+ [14]

Target

BRAF x CRAF x FLT3 x PDGFRβ x RET x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

Mechanism

BRAF inhibitors(Serine/threonine-protein kinase B-raf inhibitors), CRAF inhibitors(C-Raf kinase inhibitors), FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [6]

Active Indication

Thyroid CancerUnresectable Hepatocellular CarcinomaDifferentiated Thyroid Gland Carcinoma+ [11]

Inactive Indication

Acinar Cell Carcinomaacute leukemiaAcute Myeloid Leukemia+ [108]

Originator Organization

Onyx Pharmaceuticals, Inc.

Active Organization

Accord Healthcare SLU

Bayer AG

Novartis Pharmaceuticals Corp.

+ [5]

Inactive Organization

Bayer Healthcare Co., Ltd.

Novartis AG

Amgen, Inc.

+ [13]

Drug Highest PhaseApproved

First Approval Date

US (01 Dec 2005),

Advanced Renal Cell Carcinoma

RegulationOrphan Drug (US), Priority Review (CN), Orphan Drug (JP), Orphan Drug (EU)

Structure

Molecular FormulaC28H24ClF3N4O6S

InChIKeyIVDHYUQIDRJSTI-UHFFFAOYSA-N

CAS Registry475207-59-1

825

Clinical Trials associated with Sorafenib Tosylate

NCT06474663 / Not yet recruitingPhase 1IIT

A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias

To find the recommended dose of the drug combination cladribine, cytarabine, decitabine, and sorafenib in participants with relapsed/refractory AML, MPAL, and ALAL.

Start Date31 Dec 2024

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

NCT05669339 / RecruitingPhase 1IIT

AD HOC Trial: Artificial Intelligence-Based Drug Dosing In Hepatocellular Carcinoma

This study will test the hypothesis that a novel combination of three drugs (sorafenib, sonidegib, and irinotecan), in conjunction with individually optimized doses, can be safely administered and lead to improved clinical outcomes in patients with hepatocellular carcinoma compared to standard of care. The main objective of this study is to establish safe dose ranges for the coadministration of sorafenib, sonidegib, and irinotecan in patients with hepatocellular carcinoma. Furthermore, we will collect data to inform the application of an artificial intelligence/computational approach to individual dosing of combination chemotherapy. Individualization of dosing will be achieved by using Phenotypic Personalized Medicine (PPM) to maximize treatment efficacy in patients with hepatocellular carcinoma, while minimizing toxicity. Drug efficacy will be assessed by measuring plasma circulating tumor DNA (ctDNA). Toxicity will be assessed by quantitating organ injury and patient tolerability. Recommended dosing for future studies will be based on the totality of the data.

Start Date01 Nov 2024

Sponsor / Collaborator

University of Florida

[+1]

NCT06592989 / Not yet recruitingNot ApplicableIIT

A Clinical Study of Sorafenib Combined With Gefitinib for the Treatment of Pancreatic Neuroendocrine Tumor Patients Who Have Progressed After Previous Treatment

The incidence rate of pancreatic neuroendocrine neoplasms (pNENs) is increasing year by year. According to the statistical results of the SEER (Surveillance, Epidemiology, and End Results) database, the incidence rate of pNENs increased from 0.27/100000 to 1/100000 from 2000 to 2016, with a median overall survival time of 68 months. The 5-year overall survival rates of localized, locally advanced, and metastatic pNENs were 83%, 67%, and 28%, respectively. pNENs are gradually gaining attention and importance from the medical community. The existing therapeutic drugs for neuroendocrine tumors include somatostatin analogues, recombinant human interferon injections, chemotherapy drugs, and molecular targeted drugs.
Although these drugs can prolong patients' PFS to some extent, there is a common problem of low objective response rates. In recent years, sunitinib and everolimus have been approved for targeted therapy in patients with pancreatic neuroendocrine neoplasms , but their clinical efficacy is still limited. The study by Panzuto et al. showed that the median PFS for first-line treatment of advanced well differentiated pancreatic neuroendocrine neoplasms was 13.9 months, with an ORR of 14.9%. After imaging progression of the disease, the median PFS after second-line treatment was 15 months, and the ORR of only 5.5%. There is currently no effective treatment for patients with disease progression or drug resistance after undergoing existing treatment ways.
Therefore, there is a huge clinical demand for the treatment of pNEN patients worldwide, and effective drugs are urgently needed to benefit these patients.
Our previous research found that pathways in tumor were significantly affected in pNENs and liver metastases and EGFR tyrosine kinase inhibitor resistance and transcriptional dysregulation in tumor were unique to liver metastasis through KEGG pathway analysis; Meanwhile, GO Biological Processes analysis emphasizes those signaling pathways closely related to tyrosine phosphorylation, DNA repair, and cell cycle regulation, especially in liver metastases. Xiao et al. found that epidermal growth factor receptor (EGFR) was enriched in high glycosylation pNENs using RNA-seq. EGFR was expressed in 21.2% of pNENs using immunohistochemistry and associated with poor overall survival. Therefore, the study from Xiao et al. demonstrates that EGFR may be a potential therapeutic target for pNENs. This is consistent with our previous findings that the EGFR signaling pathway plays an important role in pNENs with liver metastases.
Due to the heterogeneity and complexity of tumors, the efficacy of monotherapy or blocking a single signaling pathway may be limited or this treatment method may easily develop drug resistance. The existing anti-tumor targeted drugs block tumor angiogenesis by inhibiting vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Colony-stimulating factor 1 receptor (CSF1R) is an important signaling pathway associated with the survival and function of tumor associated macrophages (TAMs). Inhibiting CSF1R can regulate the activity of macrophages, improve the immune microenvironment, promote immune response, and activate the body's immune function. Sofantinib is a novel oral tyrosine kinase inhibitor which exerts dual effects of anti-tumor angiogenesis and immune regulation by targeting VEGFR, FGFR1, and CSF1R, resulting in synergistic anti-tumor activity. In December 2020 and June 2021, sorafenib was approved in China as a monotherapy for unresectable locally advanced or metastatic, well differentiated extrapancreatic and pancreatic neuroendocrine neoplasms.
However, in a multicenter, single blind, open label, phase Ib/II clinical trial, the objective response rate for pNENs patients was only 19%. There is currently no effective treatment available for patients with disease progression or drug resistance after undergoing existing treatment regimens. Therefore, there is an urgent need to seek new treatment methods to improve the therapeutic effect of pNENs. Based on our previous research results and relevant literature reports, we speculate that the combination of sorafenib and EGFR inhibitor gefitinib may improve the therapeutic effect of pNENs patients.

Start Date30 Sep 2024

Sponsor / Collaborator

Shanghai First People's Hospital

100 Clinical Results associated with Sorafenib Tosylate

100 Translational Medicine associated with Sorafenib Tosylate

100 Patents (Medical) associated with Sorafenib Tosylate

10,733

Literatures (Medical) associated with Sorafenib Tosylate

01 Mar 2025·Annals of Hepatology

Camrelizumab combined with transcatheter arterial chemoembolization and sorafenib or lenvatinib for unresectable hepatocellular carcinoma: A multicenter, retrospective study

Article

Author: Li, Han ; Wang, Fei ; Su, Ke ; Liu, Yu ; Wang, Pan ; Xu, Ke ; Chi, Hao ; Jiang, Xiumei

INTRODUCTION AND OBJECTIVES:

We initiated this study to explore the efficacy of camrelizumab combined with transcatheter arterial chemoembolization (TACE) plus sorafenib or lenvatinib versus TACE plus sorafenib or Lenvatinib for unresectable hepatocellular carcinoma (HCC).

MATERIALS AND METHODS:

From June 2019 to November 2022, 127 advanced HCC patients were retrospectively analyzed in this study. This consisted of 44 patients that received camrelizumab plus TACE plus sorafenib or lenvatinib (triple therapy group) and 83 patients that received TACE plus sorafenib or lenvatinib (double treatment group). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two patient groups.

RESULTS:

Our findings demonstrated that patients received the triple therapy exhibited superior median OS (15.8 vs. 10.3 months, P=0.0011) and median PFS (7.2 vs. 5.2 months, P=0.019) compared to the double treatment group. In addition, the triple therapy group exhibited better 6-month (93.5% vs. 66.3%), 12-month (67.2% vs. 36.3%), and 24-month (17.2% vs. 7.6%) survival rates than the double treatment group. However, the ORR (43.2% vs. 28.9%, P = 0.106) and DCR (93.2% vs. 81.9%, P = 0.084) of the two groups were similar. Subgroup analysis showed that compared with the double treatment group, the triple therapy group had a better mOS for HCC with HBV (15.8 vs. 9.6 months, P = 0.0015) and tumor diameter ≥ 5cm (15.3 vs. 9.6 months, P = 0.00055).

CONCLUSIONS:

Camrelizumab plus TACE and sorafenib or lenvatinib may be a promising treatment approach for the clinical management of unresectable HCC patients.

01 Feb 2025·CURRENT CANCER DRUG TARGETS

Screening miRNAs to Hinder the Tumorigenesis of Renal Clear Cell Carcinoma Associated with KDR Expression

Article

Author: Miji, Thandaserry Vasudevan ; Suseela, Rangaraj ; Bharathi, Muruganantham ; Muthusami, Sridhar ; Almoallim, Hesham S. ; Kaviyaprabha, Rangaraj ; Thangaleela, Subramanian ; Sivakumar, Priyadarshini

Introduction::

This study delved into the role of Kinase Insert Domain Receptor (KDR) and its associated miRNAs in renal cell carcinoma through an extensive computational analysis. The potential of our findings to guide future research in this area is significant.

Methods::

Our methods, which included the use of UALCAN and GEPIA2 databases, as well as miRDB, MirDIP, miRNet v2.0, miRTargetLink, MiEAA v2.1, TarBase v8.0, INTERNET, and miRTarBass, were instrumental in identifying the regulation of miRNA associated with KDR expression. The predicted miRNA was validated with the TCGA-KIRC patients’ samples by implementing CancerMIRNome. The TargetScanHuman v8.0 was implemented to identify the associations between human miRNAs and KDR. A Patch Dock server analyzed the interactions between hsa-miR-200b-3p-KDR and hsa-miR-200b-3p with KDR.

Results::

The KDR expression rate was investigated in the Kidney Renal Cell Carcinoma (KIRC) samples, and adjacent normal tissues revealed that the expression rate was significantly higher than the normal samples, which was evident from the strong statistical significance (P = 1.63e-12). Likely, the KDR ex-pression rate was estimated as high at tumor grade 1 and gradually decreased till the metastasis grade, reducing the survival rate of the KIRC patients. To identify these signals early, we predicted a miRNA that could trigger the expression of KDR. Furthermore, we uncovered the potential associations between miR-200c-3p expressions by regulating KDR towards the progression of KIRC.

Discussion::

Upon examining the outcome, it became evident that miR-200c-3p was significantly down-regulated in KIRC compared to the normal samples. Moreover, the negative correlation was obtained for hsa-miR-200c-3p (R = - 0.276) along with the KDR expression describing that the increased rate of hsa-miR-200c-3p might reduce the KDR expression rate, which may suppress the KIRC initiation or progres-sion.

Conclusion::

The in-silico analysis indicated that the significant increase in KDR expression during the initiation of KIRC could serve as an early diagnostic marker. Moreover, KDR could be utilized to identify advancements in KIRC stages. Additionally, hsa-miR-200c-3p was identified as a potential regulator capable of downregulating and upregulating KDR expression among the 24 miRNAs screened. This find-ing holds promise for future research endeavors. Concurrent administration of the FDA-approved 5-fluor-ouracil with KIRC drugs, such as sorafenib, zidovudine, and everolimus, may have the potential to en-hance the therapeutic efficacy in downregulating hsa-miR-200c-3p. However, further in vitro studies are imperative to validate these findings and gain a comprehensive understanding of the intricate regulatory interplay involving hsa-miR-200c-3p, KDR, 5-fluorouracil, and other FDA-approved drugs for the treat-ment of KIRC. This will facilitate the identification of KIRC stage progression and its underlying pre-ventative mechanisms.

01 Feb 2025·SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

Mitochondria/lysosome dual-organelle labelling esterase probe for monitoring cell viability and evaluating lung cancer drug efficiency

Article

Author: Chen, Hua ; Hu, Bangping ; Shen, Xing-Can ; Wang, Jing ; He, Mengye ; Wang, Liping

Monitoring of cell viability plays a key role in cancer therapy and evaluation of drug efficiency. Mitochondria and lysosomes are involved in regulating cell viability in many biological processes such as apoptosis, necrosis, autophagy, and cell proliferation. Thus, there is an emerging interest in the real-time evaluation of cell viability in both mitochondria and lysosomes. Herein, for the first time, we rationally designed and developed a mitochondria/lysosome dual-organelle labelling esterase-responsive ratiometric fluorescent probe, named TMLE-2, for dual-channel monitoring of cell viability and evaluation of lung cancer drug efficiency. TMLE-2 showed dramatic ratio fluorescence changes (about 51-fold) upon reacting with esterase. Furthermore, TMLE-2 enabled visualization of mitochondria and lysosomes with red and green emission, respectively; moreover, H₂O₂-induced cell damage, sorafenib-induced ferroptosis and ascorbic-acid-mediated cell protective effects were successfully assessed by dual-organelle ratiometric fluorescent imaging and flow cytometry data. More importantly, TMLE-2 was successfully used for the first time to evaluate the efficiency of lung cancer drugs at the cellular and tissue levels based on dual-organelle esterase activity assay. In summary, the newly designed TMLE-2 is expected to have enormous potential for facilitating advancements in biomedical fields related to cell viability.

357

News (Medical) associated with Sorafenib Tosylate

21 Oct 2024

·www.globenewswire.com

Elevar Therapeutics Announces FDA Acceptance of New Drug Application Resubmission for Rivoceranib in Combination with Camrelizumab as a First-line Systemic Treatment for Unresectable Hepatocellular Carcinoma

FDA sets a PDUFA target action date of March 20, 2025Resubmission is supported by the final survival analysis of CARES-310 study, presented at ASCO 2024 FORT LEE, N.J., Oct. 21, 2024 (GLOBE NEWSWIRE) -- Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., today announced the U.S. Food and Drug Administration (FDA) accepted the resubmission of a new drug application (NDA) for its investigational drug rivoceranib, an oral VEGF-TKI, in combination with camrelizumab, a PD-1 inhibitor, as a first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma (uHCC). The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 20, 2025. “We believe rivoceranib plus camrelizumab has the potential to change the clinical practice in the first-line setting for patients with advanced liver cancer. The results of the pivotal CARES-310 trial demonstrated significant improvements in overall survival, with a very manageable safety profile compared with currently approved uHCC therapies. Elevar is committed to working with the FDA to bring this combination to market for patients and healthcare providers,” commented Chris Galloway, M.D., senior vice president of clinical and medical affairs at Elevar Therapeutics. The resubmission included the final analysis of the Phase 3 CARES-310 study presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1, which reported median overall survival (mOS) of 23.8 months, the longest mOS for any treatment in a global Phase 3 trial for patients with uHCC, confirming the combination of camrelizumab and rivoceranib continued to show sustained long-term survival as a first-line treatment for patients with uHCC.i With the efficacy results generally consistent across all subgroups, the data suggest the combination has the potential to benefit a global uHCC population. The data also demonstrated consistent efficacy across patients with both viral and non-viral etiologies. About CARES-310 The CARES-310 study, an international, randomized, open-label, Phase 3 trial, with 543 patients with uHCC who had not previously received systemic treatment was the first to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. In the primary analysis of PFS (data cut-off [DCO], May 10, 2021) and interim analysis of OS (DCO, Feb. 8, 2022), significant improvements were observed with camrelizumab (C; anti-PD-1 antibody) + rivoceranib (R; VEGFR2-TKI) vs. sorafenib (S). In the final analysis (FA) of the CARES-310 study, after an additional follow-up of ~16 months, median OS was significantly prolonged with C+R vs. S (23.8 mo [95% CI 20.6-27.2] vs. 15.2 mo [95% CI 13.2-18.5]; hazard ratio (HR) 0.64 [95% CI 0.52-0.79]; 1-sided p <0.0001). OS rate with C+R vs. S was 49.0% vs. 32.6% at 24 mo, and 37.7% vs. 24.8% at 36 mo. OS benefits with C+R was generally consistent across subgroups, regardless of geographical region, race, and etiology. Benefits in PFS, objective response rate (ORR) and duration of response (DoR) with C+R vs. S were also sustained after prolonged follow-up. Safety data aligned with the interim OS analysis, with no new signals noted. In the FA, C+R continued to show clinically meaningful survival improvement compared with S, with manageable safety. The extended follow-up further confirmed the favorable benefit-to-risk profile of C+R, supporting it as a new first-line treatment option for uHCC. About Hepatocellular Carcinoma Worldwide each year more than 800,000 people are diagnosed with liver cancerii and the disease is the cause of more than 830,000 deaths.iii Hepatocellular Carcinoma (HCC) is the most common type of liver cancer and most frequently develops in people with chronic underlying liver inflammation which may be from viral and non-viral causes. HCC typically has a poor prognosis with limited treatment options and continues to be a diagnosis with an ongoing urgent medical need. About Rivoceranib Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly selective inhibitor of vascular endothelial growth factor receptors (VEGFRs), a primary pathway for tumor angiogenesis. VEGFR inhibition is a clinically validated target to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Several clinical studies were completed in patients with uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf®). Rivoceranib, under the name apatinib (Aitan®), was the first TKI approved in gastric cancer in China (October 2014). It was also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted for gastric cancer (U.S., EU and South Korea), adenoid cystic carcinoma (U.S.) and uHCC (U.S. and EU). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), is the Chinese -territory license-holder of rivoceranib. About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer, etc.) and treatment settings. Camrelizumab, under the brand name AiRuiKa®, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021 and by the European Medicines Agency in August 2024. In October 2023, Elevar licensed camrelizumab, an anti-PD-1 antibody, for commercialization from Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) worldwide excluding Greater China and Korea. To learn more, visit ElevarTherapeutics.com. Media Contact Jeanette Bressi Head, Corporate Communications, Elevar Therapeutics jbressi@elevartherapeutics.com609-439-3997 Investor Relations Contact Wade Smith Chief Financial & Business Officer, Elevar Therapeutics wsmith@elevartherapeutics.com i CARES-310 study final analysisii Key Statistics About Liver Cancer | American Cancer Societyiii Key Statistics About Liver Cancer | American Cancer Society

Clinical ResultPhase 3Orphan DrugImmunotherapyNDA

18 Sep 2024

·www.globenewswire.com

Ipsen provides update on CONTACT-02 Phase III trial in metastatic castration-resistant prostate cancer following final overall survival analysis

Trial investigating Cabometyx® (cabozantinib) in combination with atezolizumab demonstrated a positive trend towards improvement for one of the primary endpoints of overall survival, but did not meet statistical significance Ipsen will not pursue regulatory submissions for the combination regimen in countries where we have commercialization rights (outside of the US and Japan) We remain confident in the proven profile of Cabometyx as a monotherapy and in combination with immunotherapy, across approved and potential future indications 15 September 2024 - Ipsen (Euronext: IPN; ADR: IPSEY) announced today detailed final overall survival (OS) data from the Phase III CONTACT-02 trial investigating the combination of Cabometyx® (cabozantinib) and atezolizumab in metastatic castration-resistant prostate cancer (mCRPC). The trial investigated the combination regimen versus a second novel hormonal therapy (NHT) in men previously treated with one NHT and measurable soft-tissue disease. At a median follow-up of 24.0 months, these data demonstrated a numerical but not statistically significant improvement in OS for the combination versus a second NHT (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296). As previously announced, the trial met the other primary endpoint of progression-free survival (PFS), demonstrating a statistically significant benefit in PFS.1 Safety for the combination appeared to be consistent with the known safety profiles of the individual medicines, and no new safety signals were identified. Based on the results of the final OS analysis and anticipated challenging regulatory environment in the countries in which Ipsen has commercialization rights (outside the US and Japan), Ipsen will not pursue regulatory submissions for this combination regimen in mCRPC. We remain confident, in the proven profile of Cabometyx as a monotherapy and in combination with immunotherapy across approved indications, as well as its ongoing future potential. Ipsen wishes to thank the patients, their families and healthcare teams for their participation in this clinical trial. Cabometyx (cabozantinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET and the TAM family (TYRO3, MER, AXL).2 These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis (the growth of new blood vessels that tumors need to grow), drug resistance, modulation of immune activities and maintenance of the tumor microenvironment.2,3,4,5 Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of Cabometyx outside of the U.S. and Japan. Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited (Takeda) for the commercialization and further clinical development of Cabometyx for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize Cabometyx in the U.S. In over 65 countries outside of the United States and Japan, including in the European Union, Cabometyx is currently indicated as a:3 Monotherapy for advanced renal cell carcinoma (aRCC). as first-line treatment of adults with intermediate- or poor-risk disease. in adults following prior VEGFR-targeted therapy. A combination with nivolumab for the first-line treatment of aRCC in adults. Monotherapy for the treatment of adults living with locally advanced or metastatic differentiated thyroid carcinoma, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy. Monotherapy for the treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib. The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC). Prostate cancer is the second most common cancer in men and the fourth most common cancer overall globally.6 In 2020, there were more than 1.4 million new cases of prostate cancer and about 375,300 deaths worldwide.6 Prostate cancer is considered mCRPC when it has spread beyond the prostate and does not respond to androgen-suppression therapies, a common treatment for prostate cancer.7 Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years.8 CONTACT-02 is a global, multicenter, randomized, Phase III, open-label study that enrolled 575 patients who were randomized 1:1 to the experimental arm of Cabometyx in combination with atezolizumab and the control arm of a second NHT (either abiraterone and prednisone or enzalutamide). The study included patients with mCRPC who have measurable extra-pelvic soft tissue metastasis and who have progressed on one prior NHT. The two primary endpoints of the trial are progression-free survival (PFS) and OS. The PFS analysis was conducted in the first 400 randomized patients (PFS in the intent-to-treat [ITT] population) and assessed by a blinded independent radiology committee (BIRC) per RECIST 1.1. The OS analysis was conducted in the ITT population (n=507). The secondary endpoint is objective response rate (ORR) per BIRC. The trial is sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda. Takeda is conducting the trial in Japan. More information about CONTACT-02 is available at ClinicalTrials.gov. We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 80 countries. Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com. References 1 Agarwal et al. Cabozantinib Plus Atezolizumab vs Second Novel Hormonal Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC): Primary Analyses From the Phase 3 CONTACT-02 Study. As presented at the ASCO GU congress 2024, San Francisco, USA 2 El-Khoueiry A. et al., Cabozantinib: An evolving therapy for hepatocellular carcinoma. Cancer Treatment Reviews. 2021 Jul;98:102221. DOI: 10.1016/j.ctrv.2021.102221. 3 European Medicines Agency. Cabometyx® (cabozantinib) EU Summary of Product Characteristics. Available from: https://www.ema.europa.eu/en/documents/product-information/cabometyx-epar-product-information_en.pdf. Last accessed: September 2024 4 Yakes M. et al., Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10:2298–2308. DOI: 10.1158/1535-7163.MCT-11-0264 5 Hsu et al., AXL and MET in Hepatocellular Carcinoma: A Systematic Literature Review. Liver Cancer 2021 DOI: 10.1159/000520501 6 Prostate cancer statistics. World Cancer Research Fund International. Available at: https://www.wcrf.org/cancer-trends/prostate-cancer-statistics/. Accessed August 2024 7 Prostate Cancer: Types of Treatment. Cancer.Net. Available at: https://www.cancer.net/cancer-types/prostate-cancer/types-treatment. Accessed September 2024 8 Moreira, D. M., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017; 15: 60–66.e2 The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultLicense out/inImmunotherapy

17 Sep 2024

·pmlive.com

AstraZeneca shares ‘unprecedented’ survival results for Imfinzi/Imjudo regimen in liver cancer

AstraZeneca (AZ) has shared “unprecedented” overall survival (OS) results from a late-stage study of Imfinzi (durvalumab) plus Imjudo (tremelimumab) in advanced liver cancer. The phase 3 HIMALAYA trial has been evaluating a single 300mg priming dose of Imjudo added to Imfinzi 1500mg, followed by Imfinzi every four weeks, in patients with unresectable, advanced hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were not eligible for localised treatment. The results presented at this year’s European Society for Medical Oncology Congress showed that the combination, known as the STRIDE regimen, reduced the risk of death by 24% compared to sorafenib, a standard-of-care multi-kinase inhibitor, at five years of follow-up. An estimated 19.6% of patients receiving Imfinzi plus Imjudo were alive at five years versus 9.4% of those in the sorafenib group. Additionally, in a subgroup analysis of patients who achieved disease control, 28.7% of those being treated with STRIDE were alive at five years compared to 12.7% of those in the sorafenib cohort. AZ added that an exploratory analysis showed that more patients treated with Imfinzi plus Imjudo experienced deep responses leading to longer survival compared to sorafenib, and that safety profile of the regimen was consistent with the known profiles of each medicine. Almost 900,000 people worldwide are diagnosed with liver cancer every year, with HCC accounting for the majority of cases. More than half of patients are diagnosed with advanced disease, at which point the five-year survival rate is only 7%. Imfinzi is designed to block the interaction of PD-L1 with the PD-1 and CD80 proteins, countering tumours’ immune-evading tactics and releasing the inhibition of immune responses. Meanwhile, Imjudo blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death. The combination already holds approvals to treat adults with advanced or unresectable HCC in the US, EU and several other countries. HIMALAYA lead investigator Lorenza Rimassa, Humanitas University and IRCCS Humanitas Research Hospital, said: “Treatment with [Imfinzi] plus [Imjudo] for patients with advanced liver cancer doubled the OS rate at five years, a significant survival advantage over sorafenib that has also become even more pronounced over time. “This data reinforces the use of this novel dual immunotherapy regimen and is an important milestone for patients with this devastating disease.”

Clinical ResultPhase 3ImmunotherapyDrug Approval

100 Deals associated with Sorafenib Tosylate

External Link

KEGG	Wiki	ATC	Drug Bank
D06272	Sorafenib Tosylate	L01XE05	DB00398

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Thyroid Cancer	US	Bayer HealthCare Pharmaceuticals, Inc.	22 Nov 2013
Unresectable Hepatocellular Carcinoma	US	Bayer HealthCare Pharmaceuticals, Inc.	16 Nov 2007
Differentiated Thyroid Gland Carcinoma	EU	Bayer AG	19 Jul 2006
Differentiated Thyroid Gland Carcinoma	IS	Bayer AG	19 Jul 2006
Differentiated Thyroid Gland Carcinoma	LI	Bayer AG	19 Jul 2006
Differentiated Thyroid Gland Carcinoma	NO	Bayer AG	19 Jul 2006
Hepatocellular Carcinoma	EU	Bayer AG	19 Jul 2006
Hepatocellular Carcinoma	IS	Bayer AG	19 Jul 2006
Hepatocellular Carcinoma	LI	Bayer AG	19 Jul 2006
Hepatocellular Carcinoma	NO	Bayer AG	19 Jul 2006
Renal Cell Carcinoma	EU	Bayer AG	19 Jul 2006
Renal Cell Carcinoma	IS	Bayer AG	19 Jul 2006
Renal Cell Carcinoma	LI	Bayer AG	19 Jul 2006
Renal Cell Carcinoma	NO	Bayer AG	19 Jul 2006
Advanced Renal Cell Carcinoma	US	Bayer HealthCare Pharmaceuticals, Inc.	01 Dec 2005

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia with FLT3/ITD Mutation	Phase 3	CN	Southern Medical University	20 Jun 2015
HER2-negative breast cancer	Phase 3	US	Bayer Schering Pharma AG	21 Feb 2011
HER2-negative breast cancer	Phase 3	US	Bayer Healthcare Co., Ltd.	21 Feb 2011
HER2-negative breast cancer	Phase 3	JP	Bayer Schering Pharma AG	21 Feb 2011
HER2-negative breast cancer	Phase 3	JP	Bayer Healthcare Co., Ltd.	21 Feb 2011
HER2-negative breast cancer	Phase 3	AR	Bayer Schering Pharma AG	21 Feb 2011
HER2-negative breast cancer	Phase 3	AR	Bayer Healthcare Co., Ltd.	21 Feb 2011
HER2-negative breast cancer	Phase 3	AU	Bayer Schering Pharma AG	21 Feb 2011
HER2-negative breast cancer	Phase 3	AU	Bayer Healthcare Co., Ltd.	21 Feb 2011
HER2-negative breast cancer	Phase 3	AT	Bayer Schering Pharma AG	21 Feb 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESMO2024 Manual	Not Applicable	Hepatocellular Carcinoma First line	1,361	Lenvatinib (LEN)	ujzovzxwri(uypbvqsiip) = tugvydaftm mznlvucdhz (ochtrfwlcx, 8.3 - 10.8) View more	Positive	16 Sep 2024
				Sorafenib (SOR)	ujzovzxwri(uypbvqsiip) = symxjzhvcq mznlvucdhz (ochtrfwlcx, 6.4 - 9.3) View more
ESMO2024	Not Applicable	Unresectable Hepatocellular Carcinoma	-	Nivolumab + Ipilimumab	mkwvlbcrtl(ldmfnmocpu) = fxtrztpctk vzdomugonk (wqlnvkfqjq ) View more	-	16 Sep 2024
				Lenvatinib	mkwvlbcrtl(ldmfnmocpu) = kigfpkavhk vzdomugonk (wqlnvkfqjq ) View more
ESMO_GI2024 Manual	Not Applicable	Advanced Hepatocellular Carcinoma Second line	81	Sorafenib	mxslhskxzm(ogvwpfvlfj) = lyecozhdzx fotpfgbgvi (qhauvzcqgk ) View more	-	27 Jun 2024
NCT04103398 (Pubmed) Manual	Phase 3	Hepatocellular Carcinoma	162	Sorafenib + TACE	jyqcajxudb(ndxupuecbl) = seduidsozr kjnkjfadyh (igjpqymned ) View more	Positive	20 Jun 2024
				TACE	jyqcajxudb(ndxupuecbl) = bcmhpqfcgj kjnkjfadyh (igjpqymned ) View more
NCT04039607 (CheckMate 9DW, ASCO2024) Manual	Phase 3	Unresectable Hepatocellular Carcinoma First line	668	Nivolumab + Ipilimumab	phkpyyomim(trncrdlxbh) = otqslzizre qudkbkdvlp (coeqrowbtx, 18.8 - 29.4) View more	Positive	02 Jun 2024
				Lenvatinib or Sorafenib	phkpyyomim(trncrdlxbh) = zuyyudydzl qudkbkdvlp (coeqrowbtx, 17.5 - 22.5) View more
ChiCTR1900025300 (ASCO2024) Manual	Phase 2	Unresectable Hepatocellular Carcinoma \| Portal Vein Thrombosis	90	SBRT+TACE+TKIs (sorafenib 0.4g bid; donafenib 0.2g bid; or lenvatinib 8mg/12mg qd) (Group A)	rhrwdqbkmz(sccetfffge) = epcosxgpcr szalrntlpt (qmwkmaylxv ) View more	Positive	24 May 2024
				TACE+TKIs(sorafenib 0.4g bid; donafenib 0.2g bid; or lenvatinib 8mg/12mg qd) (Group B)	rhrwdqbkmz(sccetfffge) = rqitzireui szalrntlpt (qmwkmaylxv ) View more
ASCO2024	Not Applicable	Aggressive Fibromatosis First line	40	Sorafenib <1 year	fgygjybwgh(aobiircpxw) = gduugrjgha kgxichlpmu (xfdxybfvib, 0.35 - 0.85)	Negative	24 May 2024
				Sorafenib >1 year	fgygjybwgh(aobiircpxw) = zmpytswqps kgxichlpmu (xfdxybfvib, 0.71 - 1.0)
ASCO2024	Not Applicable	Advanced Hepatocellular Carcinoma	87	Dona-TACE + Regorafenib	xtcafsxjze(mjvwxedkfb) = The Dona-TACE group received regorafenib sequentially had a lowest incidence of grade 3-4 AEs (39.1%, P<0.05) pmlevxogov (sxkbsobepk ) View more	Positive	24 May 2024
				Sora-TACE + Regorafenib
ASCO2024	Phase 2	Ewing Sarcoma	191	Cabozantinib	ksrxncgdwz(vrhozrjykl) = 8.8% hgndmxgquf (osmxxsnzdq ) View more	Positive	24 May 2024
NCT03211416 (AACR2024) Manual	Phase 1/2	Advanced Hepatocellular Carcinoma	37	Sorafenib +pembrolizumab	ainoyxpjsh(lwfvpritvw) = bnkibnmxwc gzoppgcefe (xvmrxwfhjh, 18 - 52) View more	Positive	05 Apr 2024

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