A Phase 1b Trial of Neoadjuvant Stereotactic Body Radiotherapy With or Without CCR2 Inhibitor (CCX872-B) Immunotherapy for Preoperative Treatment of Resectable Pancreatic Cancer

Standard treatment for newly diagnosed operable pancreatic cancer usually involves undergoing surgery first and then receiving chemotherapy with or without radiation therapy. However, the pancreatic cancer often comes back after this treatment. Therefore, the investigators are studying whether giving treatment prior to surgery can help decrease the risk the cancer returns.
Stereotactic Body Radiation Therapy (SBRT) is a highly focused type of radiation therapy commonly used in the treatment of pancreatic cancer. This treatment has been shown to be safe and effective for the preoperative treatment of pancreatic cancer. The purpose of this study is to determine if combining an experimental drug, CCX872-B, with SBRT continues to be safe and whether the combination treatment may be more effective at boosting the participant's immune system's ability to kill the pancreatic cancer.

Start Date01 Aug 2019

Sponsor / Collaborator-

NL-OMON42021 / CompletedNot Applicable

An open-label phase 1b study to evaluate the safety and efficacy of CCX872-B in patients with pancreatic adenocarcinoma. - Treatment of pt with pancreatic adenocarcinoma with CCX872-B.

Start Date20 Apr 2015

Sponsor / Collaborator

ChemoCentryx, Inc.

NCT02345408 / CompletedPhase 1

An Open-label Phase 1b Study to Evaluate the Safety and Efficacy of CCX872-B in Patients With Pancreatic Adenocarcinoma

This is an open-label phase 1-b study to evaluate the safety and efficacy of CCX872-B in patients with pancreatic adenocarcinoma also receiving FOLFIRINOX chemotherapy.

Start Date01 Feb 2015

Sponsor / Collaborator

ChemoCentryx, Inc.

100 Clinical Results associated with CCX-872

100 Translational Medicine associated with CCX-872

100 Patents (Medical) associated with CCX-872

Literatures (Medical) associated with CCX-872

01 Jul 2023·Journal of hepatology

FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2

Article

Author: Liu, Danfei ; Xia, Limin ; Sun, Mengyu ; Ji, Xiaoyu ; Chen, Xiaoping ; Zhang, Bixiang ; Wang, Yijun ; Liu, Bifeng ; Lin, Zhuoying ; Zhang, Zerui ; Liang, Huifang ; Xie, Meng ; Feng, Yangyang ; Huang, Wenjie ; Li, Yiwei ; Luo, Xiangyuan

BACKGROUND & AIMS:

Metastasis remains the major reason for the high mortality of patients with hepatocellular carcinoma (HCC). This study was designed to investigate the role of E-twenty-six-specific sequence variant 4 (ETV4) in promoting HCC metastasis and to explore a new combination therapy strategy for ETV4-mediated HCC metastasis.

METHODS:

PLC/PRF/5, MHCC97H, Hepa1-6, and H22 cells were used to establish orthotopic HCC models. Clodronate liposomes were used to clear macrophages in C57BL/6 mice. Gr-1 monoclonal antibody was used to clear myeloid-derived suppressor cells (MDSCs) in C57BL/6 mice. Flow cytometry and immunofluorescence were used to detect the changes of key immune cells in the tumour microenvironment.

RESULTS:

ETV4 expression was positively related to higher tumour-node-metastasis (TNM) stage, poor tumour differentiation, microvascular invasion, and poor prognosis in human HCC. Overexpression of ETV4 in HCC cells transactivated PD-L1 and CCL2 expression, which increased tumour-associated macrophage (TAM) and MDSC infiltration and inhibited CD8⁺ T-cell accumulation. Knockdown of CCL2 by lentivirus or CCR2 inhibitor CCX872 treatment impaired ETV4-induced TAM and MDSC infiltration and HCC metastasis. Furthermore, FGF19/FGFR4 and HGF/c-MET jointly upregulated ETV4 expression through the ERK1/2 pathway. Additionally, ETV4 upregulated FGFR4 expression, and downregulation of FGFR4 decreased ETV4-enhanced HCC metastasis, which created a FGF19-ETV4-FGFR4 positive feedback loop. Finally, anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib prominently inhibited FGF19-ETV4 signalling-induced HCC metastasis.

CONCLUSIONS:

ETV4 is a prognostic biomarker, and anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib may be effective strategies to inhibit HCC metastasis.

IMPACT AND IMPLICATIONS:

Here, we reported that ETV4 increased PD-L1 and chemokine CCL2 expression in HCC cells, which resulted in TAM and MDSC accumulation and CD8⁺ T-cell inhibition to facilitate HCC metastasis. More importantly, we found that anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib markedly inhibited FGF19-ETV4 signalling-mediated HCC metastasis. This preclinical study will provide a theoretical basis for the development of new combination immunotherapy strategies for patients with HCC.

01 Apr 2018·American journal of physiology. Gastrointestinal and liver physiologyQ3 · MEDICINE

CC chemokine receptor 2 promotes recruitment of myeloid cells associated with insulin resistance in nonalcoholic fatty liver disease

Q3 · MEDICINE

Article

Author: Newland, Dale ; Newsome, Philip N. ; Parker, Richard ; Ertl, Linda ; Walters, Matthew J. ; Singh, Rajinder ; McMahon, Jeff ; Adams, David H. ; Weston, Christopher J. ; Baumart, Trageen ; Miao, Zhenhua ; Ebsworth, Karen ; Armstrong, Matthew J. ; Corbett, Christopher ; Charo, Israel ; Zhang, Penglie ; Campbell, James ; Schall, Thomas J.

Nonalcoholic fatty liver disease (NAFLD) is a common disease, closely associated with obesity and insulin resistance. We investigated the presence of a subset of myeloid cells associated with metabolic disturbance in the liver of patients with NAFLD and a murine model of obesity-induced liver disease. Gene and protein expression in liver and serum was investigated with RT-PCR or ELISA and correlated to clinical disease. Liver-infiltrating immune cells were isolated from normal or diseased human liver for flow cytometric analysis. In animal experiments, mice were fed a high-fat diet (60% of calories from fat) for 16 wk, or high-fat diet with 30% fructose for 32 wk to induce steatohepatitis and fibrosis. A small molecule inhibitor of CC chemokine receptor 2 (CCR2), CCX872, was administered to some mice. A subset of CD11c+CD206+ immune cells was enriched in human liver tissue, and greater infiltration was observed in NAFLD. The presence of CD11c+CD206+ myeloid cells correlated with systemic insulin resistance. CD11c+CD206+ cells expressed high levels of CCR2, and liver CC chemokine ligand 2 (CCL2) expression was increased in nonalcoholic steatohepatitis and correlated with disease activity. In mice, CCR2 inhibition reduced infiltration of liver CD11b+CD11c+F4/80+ monocytes, which are functional homologs of human CD11c+CD206+ cells, and improved liver injury and glycemic control. A role for CCR2/CCL2 in human NAFLD has long been postulated. These data confirm a role for this chemokine/receptor axis, through mediating adipose and hepatic infiltration of myeloid cells. Inhibition of CCR2 improved hepatic inflammation and fibrosis in murine models of NAFLD. These data confirm the rationale for targeting CCR2 to treat NAFLD. NEW & NOTEWORTHY These data show for the first time that CD11c+CD206+ myeloid cells, previously associated with human adipose tissue inflammation, infiltrate into liver tissue in nonalcoholic fatty liver disease. These cells express CCR2. Inhibition of CCR2 in mice inhibits hepatic inflammation caused by a murine homolog of these myeloid cells and improves experimental liver disease.

14 Jan 2015·The Journal of neuroscience : the official journal of the Society for NeuroscienceQ1 · MEDICINE

CCR2 Antagonism Alters Brain Macrophage Polarization and Ameliorates Cognitive Dysfunction Induced by Traumatic Brain Injury

Q1 · MEDICINE

Article

Author: Susanna Rosi ; Nalin Gupta ; Cristian K. Guandique ; Sharon Liu ; Adam R. Ferguson ; Josh M. Morganti ; Timothy D. Jopson ; Lara-Kirstie Riparip

Traumatic brain injury (TBI) is a major risk factor for the development of multiple neurodegenerative diseases. With respect to the increasing prevalence of TBI, new therapeutic strategies are urgently needed that will prevent secondary damage to primarily unaffected tissue. Consistently, neuroinflammation has been implicated as a key mediator of secondary damage following the initial mechanical insult. Following injury, there is uncertainty regarding the role that accumulating CCR2+macrophages play in the injury-induced neuroinflammatory sequelae and cognitive dysfunction. UsingCX3CR1GFP/+CCR2RFP/+reporter mice, we show that TBI initiated a temporally restricted accumulation of peripherally derived CCR2+macrophages, which were concentrated in the hippocampal formation, a region necessary for learning and memory. Multivariate analysis delineated CCR2+macrophages' neuroinflammatory response while identifying a novel therapeutic treatment window. As a proof of concept, targeting CCR2+macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there was a significant reduction in multiple proinflammatory and neurotoxic mediators with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing of TBI-induced hippocampal-dependent cognitive dysfunction and reduced proinflammatory activation profile 1 month after injury. Thus, therapeutically targeting the CCR2+subset of monocytes/macrophages may provide a new avenue of clinical intervention following TBI.

News (Medical) associated with CCX-872

20 Mar 2018

·www.bioportfolio.com

ChemoCentryx Inc CCXI Pharmaceuticals Healthcare Deals and Alliances Profile [Report Updated: 27022018] Prices from USD $250

Summary ChemoCentryx Inc ChemoCentryx is a biopharmaceutical company that discovers, develops and commercializes orallyadministered therapeutics for the treatment of cancer, autoimmune diseases, and inflammatory disorders. The company's pipeline products include C5aR programs, CCR2 program, CCR9 program, and CCR1 program. ChemoCentryx's C5aR Program is for the treatment of antineutrophil cytoplasmic antibody associated renal vasculitis. The company's CCR2 Program provides CCX140 for the treatment of diabetic nephropathy, a form of kidney disease and CCX872 for the treatment of pancreatic cancer. Its CCR9 Program is for the treatment of patients with Crohn's disease and CCX507 is for the treatment of inflammatory bowel disease. ChemoCentryx is headquartered in Mountain View, California, the US. ChemoCentryx Inc CCXI Pharmaceuticals Healthcare Deals and Alliances Profile provides you comprehensive data and trend analysis of the company's Mergers and Acquisitions MAs, partnerships and financings. The report provides detailed information on Mergers and Acquisitions, Equity/Debt Offerings, Private Equity, Venture Financing and Partnership transactions recorded by the company over a five year period. The report offers detailed comparative data on the number of deals and their value categorized into deal types, subsector and regions. GlobalData derived the data presented in this report from proprietary inhouse Pharma eTrack deals database, and primary and secondary research. Scope Financial Deals Analysis of the company's financial deals including Mergers and Acquisitions, Equity/Debt Offerings, Private Equity, Venture Financing and Partnerships. Deals by Year Chart and table displaying information encompassing the number of deals and value reported by the company by year, for a five year period. Deals by Type Chart and table depicting information including the number of deals and value reported by the company by type such as Mergers and Acquisitions, Equity/Debt Offering etc. Deals by Region Chart and table presenting information on the number of deals and value reported by the company by region, which includes North America, Europe, Asia Pacific, the Middle East and Africa and South and Central America. Deals by Subsector Chart and table showing information on the number of deals and value reported by the company, by subsector. Major Deals Information on the company's major financial deals. Each such deal has a brief summary, deal type, deal rationale; and deal financials and target Company's major public companies key financial metrics and ratios. Business Description A brief description of the company's operations. Key Employees A list of the key executives of the company. Important Locations and Subsidiaries A list and contact details of key centers of operation and subsidiaries of the company. Key Competitors A list of the key competitors of the company. Key Recent Developments A brief on recent news about the company. Reasons to Buy Get detailed information on the company's financial deals that enable you to understand the company's expansion/divestiture and fund requirements The profile enables you to analyze the company's financial deals by region, by year, by business segments and by type, for a five year period. Understand the company's business segments' expansion / divestiture strategy The profile presents deals from the company's core business segments' perspective to help you understand its corporate strategy. Access elaborate information on the company's recent financial deals that enable you to understand the key deals which have shaped the company Detailed information on major recent deals includes a summary of each deal, deal type, deal rationale, deal financials and Target Company's key financial metrics and ratios. Equip yourself with detailed information about the company's operations to identify potential customers and suppliers. The profile analyzes the company's business structure, locations and subsidiaries, key executives and key competitors. Stay uptodate on the major developments affecting the company Recent developments concerning the company presented in the profile help you track important events. Gain key insights into the company for academic or business research Key elements such as break up of deals into categories and information on detailed major deals are incorporated into the profile to assist your academic or business research needs. Note*: Some sections may be missing if data is unavailable for the company.

AntibodyAcquisition

100 Deals associated with CCX-872

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic adenocarcinoma	Phase 2	US	-	01 Aug 2019
Pancreatic Cancer	Phase 2	US	ChemoCentryx, Inc.	27 Aug 2016
Diabetic Nephropathies	Preclinical	US	ChemoCentryx, Inc.	-
Glomerulosclerosis, Focal Segmental	Preclinical	US	ChemoCentryx, Inc.	-
Nonalcoholic Steatohepatitis	Preclinical	US	ChemoCentryx, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02345408 (ASCO_SITC2018)	Phase 1	Locally Advanced Pancreatic Adenocarcinoma CCL2-CCR2 signaling axis \| tumor-infiltrating macrophages	50	CCX872 QD	ciuijgycsz(uzwcaibxeo) = hdacdkxcdd rnfgrsqijm (tpjgdfaimo )	Positive	25 Jan 2018
				CCX872 BID	ciuijgycsz(uzwcaibxeo) = nkybcxbede rnfgrsqijm (tpjgdfaimo )
NCT02345408 (ASCO_GI2017)	Phase 1	Pancreatic Cancer	50	CCX872-B once daily	mjnmzdilhr(biqzxfbuax) = obcopnbonp rvsmveoyht (nmhjqnetnk ) View more	-	21 Mar 2017
				CCX872-B twice daily	mjnmzdilhr(biqzxfbuax) = nzslrbmacp rvsmveoyht (nmhjqnetnk ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

CCX-872

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation