Feasibility of CSF (Cerebrospinal Fluid) and Plasma ctDNA (Circulating Tumor Deoxyribonucleic) in BRAF (V-raf Murine Sarcoma Viral Oncogene Homolog B1)-Altered Glioma During Treatment With Plixorafenib

Evaluating the sensitivity and feasibility of using ctDNA assays optimized for detecting very low ctDNA counts from cerebrospinal fluid (CSF) and plasma. The investigators will evaluate the sensitivity of ctDNA from plasma and CSF at baseline (defined as Cycle1 Day1 (C1D1) pre-treatment) and over time in response to treatment with plixorafenib co-administered with cobicistat in BRAF-V600E mutant glioma refractory to prior therapies.

开始日期2025-01-02

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT06385119 / Recruiting临床1期

A Phase 1, Open-Label, 2-Part, Single Dose, Crossover Study to Examine the Effect of Food and Cobicistat Administration on the Pharmacokinetics and Safety of Plixorafenib in Healthy Participants.

The primary goal of this phase 1 study is to evaluate the effect of food and cobicistat on the pharmacokinetics of plixerafenib in healthy volunteers. Healthy male and female participants between the ages of 18 and 55 will be enrolled into this study. This study is looking to examine the following in two parts:
Part A
* The effect of food on the single dose PK of plixorafenib administered with cobicistat.
* The effect of cobicistat administration on the single dose PK of plixorafenib.
* The safety of plixorafenib administered alone and with cobicistat in a single dose regimen in healthy participants.
Part B
* To examine the effect of a high-fat and a low-fat meal versus fasted state on the single dose PK of plixorafenib administered alone.
* To examine the effect of a low-fat meal versus fasted state on the single dose PK of plixorafenib administered with cobicistat.
* To determine the safety of plixorafenib administered alone or with cobicistat (low-fat meal only) in a single dose regimen.

开始日期2024-04-24

申办/合作机构

Fore Biotherapeutics, Inc.

CTIS2024-513578-23-00 / Recruiting

A Phase 2 Master Protocol to assess the efficacy and safety of FORE8394,an inhibitor of BRAF class 1 and class 2 alterations, in participants withcancer harboring BRAF alterations - F8394-201

开始日期2023-07-11

申办/合作机构

Fore Biotherapeutics, Inc.

100 项与 Plixorafenib 相关的临床结果

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100 项与 Plixorafenib 相关的转化医学

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100 项与 Plixorafenib 相关的专利（医药）

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项与 Plixorafenib 相关的文献（医药）

2024-08-01·Life Science Alliance

Off-targets of BRAF inhibitors disrupt endothelial signaling and vascular barrier function

Article

作者: Zila, Nina ; Bromberger, Sophie ; Nawrocki, Arkadiusz ; Springer, Alexander ; Ressler, Julia Maria ; Zadorozhna, Yuliia ; Holzner, Silvio ; Røssel Larsen, Martin ; Schossleitner, Klaudia

Targeted therapies against mutant BRAF are effectively used in combination with MEK inhibitors (MEKi) to treat advanced melanoma. However, treatment success is affected by resistance and adverse events (AEs). Approved BRAF inhibitors (BRAFi) show high levels of target promiscuity, which can contribute to these effects. The blood vessel lining is in direct contact with high plasma concentrations of BRAFi, but effects of the inhibitors in this cell type are unknown. Hence, we aimed to characterize responses to approved BRAFi for melanoma in the vascular endothelium. We showed that clinically approved BRAFi induced a paradoxical activation of endothelial MAPK signaling. Moreover, phosphoproteomics revealed distinct sets of off-targets per inhibitor. Endothelial barrier function and junction integrity were impaired upon treatment with vemurafenib and the next-generation dimerization inhibitor PLX8394, but not with dabrafenib or encorafenib. Together, these findings provide insights into the surprisingly distinct side effects of BRAFi on endothelial signaling and functionality. Better understanding of off-target effects could help to identify molecular mechanisms behind AEs and guide the continued development of therapies for BRAF-mutant melanoma.

2024-08-01·PATHOLOGY RESEARCH AND PRACTICE

Exosomal miR-19a derived from melanoma cell promotes the vemurafenib resistance of malignant melanoma through directly targeting LRIG1 to reactivate AKT and MAPK pathway

Article

作者: Luan, Wenkang ; Lu, Xu ; Peng, Huiyong ; Rao, Min ; Shen, Xuanlin ; Ruan, Hongru

Exosomes derived from neighboring v-raf murine sarcoma viral oncogene homolog B1 inhibitor (BRAFi)-resistant melanoma cells mediate the formation of resistance in melanoma cells sensitive to BRAFi. The function and molecular mechanisms of exosomal miRNA in BRAFi resistance of melanoma have not been studied. We found that the expression of miR-19a in BRAFi resistant melanoma cells was significantly higher than that in sensitive cells, and miR-19a contributes to the resistance of melanoma cells to BRAFi by targeting immunoglobulin-like domains protein 1 (LRIG1). miR-19a was highly enriched in exosomes secreted from BRAFi resistant melanoma cells, and these exosomal miR-19a promote the spread of BRAFi resistant. The reactivation of Protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways is the main reason for the BRAFi resistant of melanoma cells. We demonstrated that exosomal miR-19a derived from melanoma cell promotes the formation and spread of BRAFi resistant in melanoma through targeting LRIG1 to reactivate AKT and MAPK pathway. Therefore, miR-19a may serve as a potential therapeutic target in melanoma patients with acquired drug resistance.

2023-12-01·Oncogene

Inhibition of TGF-β signaling, invasion, and growth of cutaneous squamous cell carcinoma by PLX8394

Article

作者: Heino, Jyrki ; Nissinen, Liisa ; Riihilä, Pilvi ; Siljamäki, Elina ; Suwal, Ujjwal ; Rappu, Pekka ; Kähäri, Veli-Matti ; Kallajoki, Markku

Abstract:

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. The prognosis of patients with metastatic cSCC is poor emphasizing the need for new therapies. We have previously reported that the activation of Ras/MEK/ERK1/2 and transforming growth factor β (TGF-β)/Smad2 signaling in transformed keratinocytes and cSCC cells leads to increased accumulation of laminin-332 and accelerated invasion. Here, we show that the next-generation B-Raf inhibitor PLX8394 blocks TGF-β signaling in ras-transformed metastatic epidermal keratinocytes (RT3 cells) harboring wild-type B-Raf and hyperactive Ras. PLX8394 decreased phosphorylation of TGF-β receptor II and Smad2, as well as p38 activity, MMP-1 and MMP-13 synthesis, and laminin-332 accumulation. PLX8394 significantly inhibited the growth of human cSCC tumors and in vivo collagen degradation in xenograft model. In conclusion, our data indicate that PLX8394 inhibits several serine-threonine kinases in malignantly transformed human keratinocytes and cSCC cells and inhibits cSCC invasion and tumor growth in vitro and in vivo. We identify PLX8394 as a potential therapeutic compound for advanced human cSCC.

项与 Plixorafenib 相关的新闻（医药）

2024-12-05

·Business Wire

FORE Biotherapeutics to Participate in the Wells Fargo Virtual Private Biotech Symposium

PHILADELPHIA--( BUSINESS WIRE )--FORE Biotherapeutics today announced that the Company will participate in the Wells Fargo Virtual Private Biotech Symposium on Thursday, December 12. William Hinshaw, Chief Executive Officer and Michael Byrnes, Chief Financial Officer, will host and participate in one-on-one meetings. Please contact Argot Partners to schedule one-on-one meetings with the management team. About FORE Biotherapeutics Fore is a registration stage targeted oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394; formerly PLX8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1 st and 2 nd generation BRAF inhibitors. Plixorafenib has demonstrated single-agent efficacy signals across a variety of tumor types with a manageable safety profile in a Phase 1/2a clinical trial of over 100 patients and is currently enrolling patients in a clinical trial with registrational intent in three distinct indications. For more information, please visit www.fore.bio or follow us on X and LinkedIn .

临床1期

2024-11-07

·Business Wire

FORE Biotherapeutics to Participate in Upcoming November Conferences

PHILADELPHIA--( BUSINESS WIRE )--FORE Biotherapeutics today announced that the Company will participate at the following investor conferences: Stifel 2024 Healthcare Conference. The Company will attend on Monday, November 18, and will provide a corporate presentation at 2:25 p.m. – 2:55 p.m. ET. Jefferies London Healthcare Conference. The Company will attend and participate in one-on-one meetings on Wednesday, November 20, and Thursday, November 21. Management will host and participate in one-on-one meetings. Please contact Argot Partners to schedule one-on-one meetings with the management team. About FORE Biotherapeutics Fore is a registration stage targeted oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394; formerly PLX8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1 st and 2 nd generation BRAF inhibitors. Plixorafenib has demonstrated single-agent efficacy signals across a variety of tumor types with a manageable safety profile in a Phase 1/2a clinical trial of over 100 patients and is currently enrolling patients in a clinical trial with registrational intent in three distinct indications. For more information, please visit www.fore.bio or follow us on X and LinkedIn .

2024-09-04

·Business Wire

FORE Biotherapeutics to Participate in Upcoming Investor Conferences

PHILADELPHIA--( BUSINESS WIRE )--FORE Biotherapeutics today announced that the Company, will participate at the following investor conferences: Cantor 2024 Global Healthcare Conference. The Company will attend and participate in one-on-one meetings on Wednesday, September 18. UBS 2024 Virtual Biotechnology Private Company Symposium. The Company will attend on Thursday, September 19, and will provide a corporate presentation from 10:00 a.m. – 10:25 a.m. ET. Bank of America Healthcare Trailblazers Private Company Conference. The Company will attend and participate in one-on-one meetings on Wednesday, September 25. RBC Capital Markets 2024 Virtual Biotechnology Private Company Conference. The Company will attend on Tuesday, October 1, and will sit for a fireside chat from 10:40 a.m. – 11:10 a.m. ET. Management will host and participate in one-on-one meetings. Please contact Argot Partners to schedule one-on-one meetings with the management team. About FORE Biotherapeutics Fore Bio is a precision oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394; formerly PLX8394) is a V600 and non-V600 BRAF inhibitor with manageable clinical safety and early efficacy signals in an ongoing Phase 1/2a clinical trial. The Fore Bio research and development team is optimizing drug development by identifying existing compounds with known clinical profiles and a clear path through clinical development to advance new medicines for patients without treatment options. For more information, please visit www.fore.bio or follow us on X (formerly Twitter) and LinkedIn .

100 项与 Plixorafenib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16038

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
BRAF突变实体瘤	临床2期	美国	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	加拿大	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	法国	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	德国	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	意大利	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	韩国	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	西班牙	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	瑞典	Fore Biotherapeutics, Inc.	2023-02-21
BRAF突变实体瘤	临床2期	英国	Fore Biotherapeutics, Inc.	2023-02-21
胶质瘤	临床2期	美国	Fore Biotherapeutics, Inc.	2015-04-01