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 CarcinomaAdvanced Hepatocellular Carcinoma+ [11]

Inactive Indication

Acinar Cell Carcinomaacute leukemiaAcute Myeloid Leukemia+ [117]

Originator Organization

Onyx Pharmaceuticals, Inc.

Active Organization

Novartis Pharmaceuticals Corp.

Bayer AG

Merck Sharp & Dohme Corp.

+ [7]

Inactive Organization

Bayer Healthcare Co., Ltd.

Genzyme Corp.Laboratoire Pierre Fabre Oncologie

+ [12]

Drug Highest PhaseApproved

First Approval Date

US (01 Dec 2005),

Advanced Renal Cell Carcinoma

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

Structure/Sequence

Molecular FormulaC28H24ClF3N4O6S

InChIKeyIVDHYUQIDRJSTI-UHFFFAOYSA-N

CAS Registry475207-59-1

800

Clinical Trials associated with Sorafenib Tosylate

NCT06797427

/ Not yet recruitingEarly Phase 1

An Open-label, Prospective, Randomised, Cross-over Trial to Assess the Pharmacokinetics of an Amorphous Formulation of Sorafenib in Mesoporous Magnesium Carbonate (DPH001) Compared to Nexavar® (sorafenib) in Healthy Volunteers

The study aims to assess the pharmacokinetics and safety of DPH001, an amorphous formulation of sorafenib, compared to Nexavar® in healthy volunteers.

Start Date10 Feb 2025

Sponsor / Collaborator

Disruptive Pharma ABStartup

[+1]

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 Date02 Dec 2024

Sponsor / Collaborator

University of Florida

[+1]

NCT06309485

/ Not yet recruitingPhase 2

An Open-Label Phase 2 Study of WGI-0301 Plus Sorafenib in Patients With Advanced Hepatocellular Carcinoma as Second Line Therapy

The purpose of this study is to determine the MTD of WGI-0301 in combination with Sorafenib for advanced Hepatocellular Carcinoma (HCC) and assess its safety and efficacy in adults with advanced unresectable HCC who have previously received PD-1 / PD-L1 immune checkpoint inhibitors.

Start Date01 Aug 2024

Sponsor / Collaborator

Zhejiang Haichang Bio-Tech Co., Ltd.

100 Clinical Results associated with Sorafenib Tosylate

100 Translational Medicine associated with Sorafenib Tosylate

100 Patents (Medical) associated with Sorafenib Tosylate

16,092

Literatures (Medical) associated with Sorafenib Tosylate

01 Dec 2025·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Absorption, metabolism, and excretion of oral [14C] radiolabeled donafenib: an open-label, phase I, single-dose study in humans

Article

Author: Zhang, Cong ; Li, Chengwei ; Lv, Binhua ; Bian, YiCong ; Miao, Liyan ; Yi, Ling ; Ma, Sheng ; Zhang, Hua

PURPOSE:

The study aims to investigate the absorption, metabolism, and excretion of donafenib, a deuterated derivative of sorafenib, in healthy Chinese male volunteers.

METHODS:

Six healthy Chinese male volunteers were administered a single oral dose of 300 mg donafenib containing 120 µCi of [14 C]-donafenib. The study involved collecting and analyzing plasma, urine, and feces samples to determine the recovery and distribution of total radioactivity, identify metabolites, and assess the metabolic pathways of donafenib.

RESULTS:

The mean recovery of total radioactivity was 97.31% of the administered dose. Six metabolites were identified, with the parent drug being the major radioactive component in plasma (67.52% of total radioactivity) and feces (83.17% of the dose). The N-oxidation metabolite (M2) was prominent in plasma. Donafenib was predominantly excreted via feces, indicating liver metabolism, with minimal renal excretion. The metabolic pathways of donafenib were similar to those of sorafenib, but the metabolite profiles differed significantly. Notably, the amide hydrolysis metabolite M6, present in sorafenib, was absent in donafenib.

CONCLUSION:

Donafenib is primarily metabolized in the liver and excreted through feces, with a metabolic profile that differs from sorafenib due to the deuterium isotope effect. These differences in metabolic characteristics may contribute to donafenib's improved safety and efficacy as a treatment for advanced hepatocellular carcinoma (HCC).

01 Apr 2025·COMPUTATIONAL BIOLOGY AND CHEMISTRY

Machine learning and molecular subtyping reveal the impact of diverse patterns of cell death on the prognosis and treatment of hepatocellular carcinoma

Article

Author: Yan, Xinyue ; Ji, Lurao ; Li, Xiaoqin ; Wang, Meng ; Gao, Bin

Programmed cell death (PCD) is a significant factor in the progression of hepatocellular carcinoma (HCC) and might serve as a crucial marker for predicting HCC prognosis and therapy response. However, the classification of HCC based on diverse PCD patterns requires further investigation. This study identified a novel molecular classification named PCD subtype (C1, C2, and C3) based on the genes associated with 19 PCD patterns, distinguished by clinical, biological functional pathways, mutations, immune characteristics, and drug sensitivity. Validated in 4 independent datasets, diverse cell death pathways were enriched in the C3 subtype, including apoptosis, pyroptosis, and autophagy, it also exhibited a highly infiltrative immunosuppressive microenvironment and demonstrated higher sensitivity to compounds such as Paclitaxel, Bortezomib, and YK-4-279, while C1 subtype was significantly enriched in cuproptosis and metabolism-related pathways, suggesting that it may be more suitable for cuproptosis-inducing agent therapy. Subsequently, utilizing the machine learning algorithms, we constructed a cell death-related index (CDRI) with 22 gene features and constructed prognostic nomograms with high predictive performance by combining CDRI with clinical features. Notably, we found that CDRI effectively predicted the response of HCC patients to therapeutic strategies, where patients with high CDRI were more suitable for sorafenib drug therapy and patients with low CDRI were more ideal for transarterial chemoembolization (TACE). In conclusion, the PCD subtype and CDRI demonstrate significant efficacy in predicting the prognosis and therapeutic outcomes for patients with HCC. These findings offer valuable insights for the development of precise, individualized treatment strategies.

01 Apr 2025·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Lipid core-chitosan shell hybrid nanoparticles for enhanced oral bioavailability of sorafenib

Article

Author: Vo, Dang-Khoa ; Gul, Maleeha ; Kim, Wondong ; Choi, Ho-Ik ; Maeng, Han-Joo ; Kim, Jin-Ki ; Ansari, Muhammad Mohsin ; Noh, Ha-Yeon ; Nguyen, Thu-Hang ; Zeb, Alam ; Sahar, Najam Us ; Ryu, Jeong-Su

Limited aqueous solubility is a major hurdle resulting in poor and variable oral bioavailability, high doses, side effects, and the suboptimal therapeutic efficacy of sorafenib (SRF). In this study, we developed SRF-loaded solid lipid nanoparticles (SRF-SLNs) and lipid core-chitosan shell hybrid nanoparticles (CS-SRF-SLNs) to improve the oral absorption of SRF. SRF-SLNs were prepared using a stearyl alcohol core stabilized with a surfactant mixture, followed by surface decoration with chitosan to form CS-SRF-SLNs. The developed SRF-SLNs and CS-SRF-SLNs displayed uniform and well-separated spherical particles with small particle size (112.2 and 124.6 nm), low PDI (0.114 and 0.148), adequate zeta potential (-18.6 and +21.2 mV) and high encapsulation efficiency (92.0 and 91 %). Thermal and crystallinity studies (DSC and PXRD) confirmed the successful incorporation of SRF into the lipid matrix and its conversion to the amorphous state. The CS-SRF-SLNs demonstrated sustained SRF release in simulated gastric and intestinal fluids with improved aqueous solubility. Following oral administration to rats, CS-SRF-SLNs significantly improved SRF bioavailability compared with SRF-SLNs and SRF dispersion. Collectively, CS-SRF-SLNs were found to be superior to SRF-SLNs owing to their better sustained-release profile and pharmacokinetic parameters, thereby demonstrating their usefulness for oral delivery by minimizing the solubility-related issues of SRF.

383

News (Medical) associated with Sorafenib Tosylate

07 Jan 2025

·endpts.com

Drugmakers cut some list prices, shrinking room for rebates in cancer, asthma and diabetes

Bayer’s Nexavar and Boehringer Ingelheim’s Spiriva are among a handful of drugs with reduced US list prices for the new year, according to a Tuesday analysis that showed average prices growing at their slowest rate in years. Bayer cut the list price of its cancer drug Nexavar in half, effective Jan. 1, according to data compiled by Drug Channels Institute (DCI). The list prices for Merck’s diabetes drugs Janumet XR and Januvia were cut by 42.4%. And Boehringer reduced the list price of its asthma drug Spiriva by 36.7% and Atrovent, which is used to treat chronic obstructive pulmonary disease, by 35.0%. On average, list prices last year for brand-name drugs grew at their lowest rate in a decade, according to the analysis. In 2024, they were up 2.3%, compared with 5% between 2019 and 2024, according to Drug Channels. Most patients don’t pay list prices, which are used as a starting point for negotiations with insurers, who typically pay a far lower net price, pocketing some of the difference in the form of rebates that can be used as incentives to prefer one drug over another. Those rebates have become an increasingly powerful force in price negotiations over the years, though they have also caused significant scrutiny of the insurance and pharmacy benefit management industry. And as list prices have risen, the handful of patients who buy drugs without insurance, or who pay a percentage of the list price, have faced financial pain from that dynamic. The shift to reduced list prices may partly be drugmakers’ reaction to the Inflation Reduction Act, which for the first time allows the federal government to directly negotiate drug prices with manufacturers. The law targets drugs with high Medicare spending based on list costs. That could “encourage manufacturers to narrow large gross-to-net gaps so as to bypass a drug’s selection by CMS,” DCI president Adam Fein said in his analysis. But Fein told Endpoints News Tuesday that the IRA won’t necessarily reduce the gross-to-net price gap for drugs not part of the negotiation process. He said that the law will still “encourage Part D plans to prefer high-list, high-rebate specialty drugs, even as the government and manufacturers will prefer a low list-price version.” A Merck spokesperson said the company lowered the list prices of its diabetes drugs to “align the list price more closely to the net price.” The price decrease is “unrelated” to the Medicare drug price negotiation process, the spokesperson said. Januvia was included in a list of drugs to face negotiations last year. The Centers for Medicare & Medicaid Services is slated to announce the second round of drugs selected for negotiation by Feb. 1. A Boehringer spokesperson said list price reductions are part of its “normal business practices” and that its action reflects the company’s “ongoing commitment to patient affordability and access.” A representative for Bayer didn’t immediately respond to a request for comment. Bayer’s and Boehringer’s drugs were not included in last year’s IRA list. Editor’s note: Updates article with comment from Boehringer.

23 Dec 2024

·pipelinereview.com

Bristol Myers Squibb Receives European Commission Approval for Opdivo® (nivolumab) plus Yervoy® (ipilimumab) for the First-Line Treatment of Adult Patients with Microsatellite Instability–High or Mismatch Repair Deficient Metastatic Colorectal Cancer

Approval based on results of the Phase 3 CheckMate -8HW trial, in which the dual immunotherapy combination of Opdivo plus Yervoy demonstrated statistically significant and clinically meaningful reduction in the risk of disease progression or death compared to investigator’s choice of chemotherapy With this approval, Opdivo plus Yervoy is the first dual checkpoint inhibitor treatment approved in the European Union for the first-line treatment of MSI-H/dMMR mCRC PRINCETON, NJ, USA I December 23, 2024 I Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo ® (nivolumab) plus Yervoy ® (ipilimumab)for the first-line treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC). “Colorectal cancer is the second leading cause of cancer death in Europe and patients are in need of new treatment options that delay disease progression. Approximately 5-7% of metastatic colorectal cancer patients have MSI-H/dMMR tumors and these patients are less likely to benefit from conventional chemotherapy and typically have poor prognosis outcomes,” said Dana Walker, M.D., M.S.C.E., vice president, Opdivo global program lead, Bristol Myers Squibb. “The EC’s decision to approve Opdivo plus Yervoy represents a significant milestone for this patient population in the European Union and underscores our commitment to advancing treatment options.” The decision is based on results from the CheckMate -8HW trial, which were presented at medical congresses earlier this year. These data formed the basis for the Company’s application to the European Medicines Agency (EMA) . In the study, Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoint of progression-free survival (PFS) and reduced the risk of disease progression or death by 79% compared to the investigator’s choice of chemotherapy as assessed by Blinded Independent Central Review (BICR). The safety profile for the dual immunotherapy combination remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. This approval by the EC for Opdivo plus Yervoy for the first-line treatment of adult patients with MSI-H or dMMR unresectable or mCRC is valid in all 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. In addition to approval in colorectal cancer, Opdivo- based options are also approved for treatment of multiple tumor types in the EU. Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial. CheckMate -8HW and Select Efficacy and Safety Results With a median follow-up of approximately 31.5 months, CheckMate -8HW trial results showed: About CheckMate -8HW CheckMate -8HW (NCT04008030) is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or the investigator’s choice of chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC). 839 patients were randomized to receive either Opdivo monotherapy ( Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W ), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first-line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. Further data disclosure is planned at The American Society of Clinical Oncology Gastrointestinal Cancers Symposium taking place January 23, 2025, through January 25, 2025. The trial also evaluates several secondary safety and efficacy endpoints, including overall survival, which is ongoing. About dMMR or MSI-H Colorectal Cancer Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined. Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors. These patients are less likely to benefit from conventional chemotherapy and typically have a poor prognosis. Bristol Myers Squibb: Creating a Better Future for People with Cancer Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. About Opdivo Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo ’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression. In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union. About Yervoy Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. INDICATIONS OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC). OPDIVO® (nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO® (nivolumab) as adjuvant treatment after surgery. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO® (nivolumab). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC). OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Please see US Full Prescribing Information for OPDIVO and YERVOY . Clinical Trials and Patient Populations Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238–adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma in combination with chemotherapy; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma combination with YERVOY; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 77T–Neoadjuvant treatment with platinum-doublet chemotherapy for non-small cell lung cancer followed by single-agent OPDIVO as adjuvant treatment after surgery; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymph. About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , X (formerly Twitter), YouTube , Facebook and Instagram . SOURCE: Bristol Myers Squibb

Clinical ResultImmunotherapyDrug ApprovalPhase 3ASCO

18 Dec 2024

·www.globenewswire.com

Coherus to Present Final Phase 2 Casdozokitug Combination Data in Patients with Metastatic Hepatocellular Carcinoma at ASCO-GI 2025

- Randomized Phase 2 study initiated evaluating the combination of casdozokitug, toripalimab and bevacizumab in patients with liver cancer - REDWOOD CITY, Calif., Dec. 18, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (“Coherus,” NASDAQ: CHRS) today announced that an abstract highlighting final clinical and biomarker data from its Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-antagonistic antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC), has been selected for a poster presentation at the upcoming 2025 ASCO GI Annual Meeting, being held January 23-25, 2025, in San Fransisco, CA. “Casdozo is a first-in-class antibody, and in oncology, is the first IL-27 cytokine antagonist to demonstrate monotherapy responses and immune activation with a safety profile that lends itself to combination,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “We look forward to sharing the final data from this Phase 2 combination study of casdozo with standard of care with the medical community at the upcoming 2025 ASCO-GI annual meeting. We now have data across several tumor types for casdozo demonstrating clinical activity. We are particularly excited about HCC given the strong preclinical package for targeting IL-27 in liver cancer and now translation to the clinic.” Coherus has initiated a new randomized Phase 2 study (NCT06679985) evaluating casdozo, in combination with bevacizumab and toripalimab, Coherus’ next-generation anti-PD-1 monoclonal antibody, in participants with first-line HCC. This randomized, parallel, open-label Phase 2 study is designed to evaluate the safety, efficacy, and Project Optimus1 dosing of the triplet combination. The study is expected to enroll up to 72 patients, who will be randomized to receive one of two biologically active doses of casdozo with toripalimab plus bevacizumab or toripalimab plus bevacizumab without casdozo. “Advancing casdozo development in first-line HCC with a randomized Phase 2 combination study marks a significant milestone in our strategic path to progress our clinical pipeline, which is focused on overcoming immune suppression in the tumor microenvironment to extend survival and improve outcomes for patients and pursuing new indications for toripalimab in the U.S.,” continued Dr. Dias. “Casdozo has shown encouraging responses in the first line setting when added to the existing standard of care, atezolizumab and bevacizumab, and we’re excited to build upon these data with this new Phase 2 study evaluating casdozo in combination with toripalimab and bevacizumab.” In the Phase 3 HEPATORCH study, conducted by Junshi Biosciences, patients with advanced HCC treated with toripalimab combined with bevacizumab as a first-line therapy showed significantly better clinical efficacy than sorafenib monotherapy.2 HEPATORCH patients showed an objective response rate of 25.3% versus 6.1% in the sorafenib group, a median progression-free survival of 5.8 months, and a median overall survival of 20 months, compared to 4 and 14.5 months, respectively, for the sorafenib group.3 Toripalimab in combination with bevacizumab was well tolerated, with a toxicity profile consistent with the known toxicity profile of each monotherapy, with no new safety signals identified.3 The results of the HEPATORCH study support the clinical study of toripalimab in combination with bevacizumab as a new first-line treatment option for advanced HCC which, along with the results from the Phase 2 casdozo study reported to date, support pursuing a triple combination of casdozo with toripalimab plus bevacizumab in patients with advanced or metastatic HCC. ASCO-GI 2025 Presentation Details Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC) Lead Author: Daneng Li, City of Hope National Comprehensive Cancer CenterAbstract #: 605Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary TractDate and Time: Friday, January 24, 2025; 11:30 a.m. – 1:00 p.m. PT Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma; HCC), gall bladder, and bile ducts (collectively called biliary tract cancers). The most common type of primary liver cancer in adults is HCC (accounting for ~90%), which is the third leading cause of cancer-related deaths worldwide. According to the NCI Surveillance, Epidemiology and End Results Program (SEER), there will be an estimated 41,630 new cases and 29,840 deaths from liver and intrahepatic bile duct cancer in the US in 2024.4 The U.S. 5-year relative survival rate for liver and intrahepatic bile duct cancer is 21.7%.4 The liver cancer treatment pattern has changed in recent years with the emergence of immunotherapy combinations and will continue to evolve as more treatment options become available for these highly lethal cancers. About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that is expected to be synergistic with toripalimab and its proven commercial capabilities in oncology. Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust antitumor immunologic response and enhance outcomes for patients with cancer, particularly patients underserved by current immunotherapy treatments. Casdozokitug is a novel IL-27 antagonistic antibody being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors, including HNSCC. CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). An IND for CHS-1000 was allowed to proceed by the FDA in the second quarter of 2024 and proceeding to the first-in-human clinical study is subject to further evaluation in our portfolio prioritization process. Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, and UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta. In December 2024, Coherus announced that it entered into an agreement for the divestiture of the UDENYCA franchise. The proposed transaction is expected to close by the end of the first quarter of 2025. Neulasta® is a registered trademark of Amgen, Inc. Forward-Looking Statements Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Coherus’ expectations about identifying synergies between its I-O pipeline and its commercial operations and its I-O pipeline and toripalimab; future enrollment estimates for Coherus’ clinical studies; Coherus’ expectations that it will be able to demonstrate that its clinical pipeline candidates can extend patient survival; and the ability to satisfy the closing conditions to consummate the proposed transaction for the divestiture of the UDENYCA franchise at all or in the estimated time. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance or achievements to differ significantly from any future results, performance or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the clinical drug development process; risks related to Coherus’ existing and potential collaboration partners; risks of Coherus’ reliance on third-parties; the risks and uncertainties related to manufacturing and supply of Coherus’ products, the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus’ regulatory filings; uncertainties as to the timing for completion of the proposed transaction; uncertainties as to the Company’s ability to obtain the approval of its shareholders required to consummate the proposed transaction for the divestiture of UDENYCA; the possibility that competing offers will be made by third parties; the occurrence of any event, change or other circumstance that may give rise to a right of one or both parties to terminate the agreement to divest UDENYCA; the possibility that the proposed transaction for the divestiture of UDENYCA may not be completed in the time frame expected by the Company or at all, including due to the possibility that a governmental entity may prohibit, delay, or refuse to grant approval, if required, for the consummation of the proposed transaction to divest UDENYCA (or only grant approval subject to adverse conditions or limitations). All forward-looking statements contained in this press release speak only as of the date of this press release. Unless required by law, the Company is not under any duty and undertakes no obligation to publicly update or revise any forward-looking statement to reflect changes in underlying assumptions or factors, of new information, data or methods, future events or other changes. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2024 filed with the Securities and Exchange Commission on November 6, 2024, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission including, when available, the proxy statement of the Company relating to the proposed transaction for the divestiture of UDENYCA. UDENYCA® and LOQTORZI®, whether or not appearing in large print or with the trademark symbol, are trademarks of Coherus, its affiliates, related companies or its licensors or joint venture partners unless otherwise noted. Trademarks and trade names of other companies appearing in this press release are, to the knowledge of Coherus, the property of their respective owners. Coherus Contact Information:For Investors:Jodi SieversVP, Investor Relations & Corporate CommunicationsIR@coherus.com For Media:Argot Partners(212) 600-1902coherus@argotpartners.com 1Project Optimus: Reforming the dose optimization and dose selection paradigm in oncology 2Shanghai Junshi Biosciences Co., Ltd (2024, June 11) Junshi Biosciences Announces Phase 3 Study of Toripalimab Combined with Bevacizumab for the First-line Treatment of Advanced Hepatocellular Carcinoma Meets Primary Endpoint 3FAN, J. (2024) HEPATORCH: A randomized, open-label, multicenter, phase III clinical study of the safety and efficacy of toripalimab combined with bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma presented at the 2024 Annual Meeting of Chinese Society of Clinical Oncology 4National Cancer Institute Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer; retrieved December 17, 2024, from https://seer.cancer.gov/statfacts/html/livibd.html

Phase 2Clinical ResultImmunotherapyPhase 3ASCO

100 Deals associated with Sorafenib Tosylate

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KEGG	Wiki	ATC	Drug Bank
D06272	Sorafenib Tosylate	L01XE05	DB00398

R&D Status

Approved

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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
Advanced Hepatocellular Carcinoma	AU	Bayer Australia Ltd.	27 Sep 2006
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

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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 Healthcare Co., Ltd.	21 Feb 2011
HER2-negative breast cancer	Phase 3	US	Bayer Schering Pharma AG	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

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Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CTNI-45 (SNO2024)	Phase 2	Recurrent Malignant Glioma GRP78 (HSPA5) \| PDGFRa	33	Sorafenib	voydchsdqs(tarmmtpktk) = one grade 3 toxicity for maculopapular rash (6.4%) hkfwvlcoes (ngdpwdbrey ) View more	Positive	11 Nov 2024
ESMO2024 Manual	Not Applicable	Hepatocellular Carcinoma First line	1,361	Lenvatinib (LEN)	evmphboylx(ladxwkbksz) = kbeqjzwiwo ewvmyxcnut (sgfgekfldq, 8.3 - 10.8) View more	Positive	16 Sep 2024
				Sorafenib (SOR)	evmphboylx(ladxwkbksz) = ukmkpfkvtu ewvmyxcnut (sgfgekfldq, 6.4 - 9.3) View more
NCT04039607 (ESMO2024)	Phase 3	Unresectable Hepatocellular Carcinoma	-	Nivolumab + Ipilimumab	ukeaotfyph(bjlnqievwi) = ttrpdwidwk fvwrsxajqr (kptiindlwc ) View more	-	16 Sep 2024
				Lenvatinib	ukeaotfyph(bjlnqievwi) = vvukglzuai fvwrsxajqr (kptiindlwc ) View more
ESMO_GI2024 Manual	Not Applicable	Advanced Hepatocellular Carcinoma Second line	81	Sorafenib	cukioyawen(egjtmpoxao) = ucrphymdib kcqvqtolbl (gekjuvsigs ) View more	-	27 Jun 2024
NCT04103398 (Pubmed) Manual	Phase 3	Hepatocellular Carcinoma	162	Sorafenib plus TACE	xtodtrpsok(zspedwlpfa) = afbpmcqmet pscwwwacjk (igeymhuwho ) View more	Positive	20 Jun 2024
				TACE alone	xtodtrpsok(zspedwlpfa) = liizuchgbh pscwwwacjk (igeymhuwho ) View more
NCT04039607 (CheckMate 9DW, ASCO2024) Manual	Phase 3	Unresectable Hepatocellular Carcinoma First line	668	Nivolumab + Ipilimumab	wastfytlnd(effdkdvpmn) = alvfkyvdoc ctmjitkmiv (wevobfbmhb, 18.8 - 29.4) View more	Positive	02 Jun 2024
				Lenvatinib or Sorafenib	wastfytlnd(effdkdvpmn) = gftgrtxois ctmjitkmiv (wevobfbmhb, 17.5 - 22.5) View more
ChiCTR1900025300 (ASCO2024) Manual	Phase 2	Unresectable Hepatocellular Carcinoma \| Portal Vein Thrombosis	90	SBRT+TACE+TKIssorafenib	actlubxlkc(shryyvlnuz) = phalxvegtq xoyxyzzuii (rvfqjpbwxk ) View more	Positive	24 May 2024
				TACE+TKIssorafenib	actlubxlkc(shryyvlnuz) = sivpwkzztw xoyxyzzuii (rvfqjpbwxk ) View more
ASCO2024	Not Applicable	Aggressive Fibromatosis First line	40	Sorafenib <1 year	kwunuyessh(euvpnlhfis) = hvtytfvtvs vlfhqhxmdo (tuknfzlbhm, 0.35 - 0.85)	Negative	24 May 2024
				Sorafenib >1 year	kwunuyessh(euvpnlhfis) = oibfmbwxgt vlfhqhxmdo (tuknfzlbhm, 0.71 - 1.0)
ASCO2024	Phase 2	Ewing Sarcoma	191	Cabozantinib	auborppjqr(xidefdxnwo) = 8.8% pptlghstbt (wwfjsjymxz ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Advanced Hepatocellular Carcinoma	87	Dona-TACE + Regorafenib	xtmzzvubyz(tkqrmcyqjv) = The Dona-TACE group received regorafenib sequentially had a lowest incidence of grade 3-4 AEs (39.1%, P<0.05) vgoyvnlpfq (yucludpgsb ) View more	Positive	24 May 2024
				Sora-TACE + Regorafenib

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