FibroGen today announced that an open-label, phase 1 clinical trial designed to evaluate the safety and tolerability of FG-3019 in combination with gemcitabine and erlotinib in patients with locally advanced or metastatic pancreatic cancer has commenced
San Francisco, CA, USA | December 15, 2008 | FibroGen, Inc. today announced that an open-label, phase 1 clinical trial designed to evaluate the safety and tolerability of FG-3019, a fully human monoclonal antibody against connective tissue growth factor (CTGF), in combination with gemcitabine and erlotinib in patients with locally advanced or metastatic pancreatic cancer has commenced.
The study is an open-label, dose-escalation trial expected to enroll up to 18 patients and to test three dose levels of FG-3019 administered via infusion every two weeks. After the second administration of FG-3019, patients will initiate treatment with gemcitabine (Gemzar®) and erlotinib (Tarceva®). Patients will continue on FG-3019 treatment until disease progression as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary objectives of the study are to evaluate the activity and pharmacokinetics of FG-3019 in combination with gemcitabine and erlotinib.
The study is being conducted at two sites: at Stanford University School of Medicine, Stanford, CA, where Albert C. Koong, MD, Ph.D., is Principal Investigator and at Dartmouth Hitchcock Medical Center, Lebanon, NH, where Marc J. Pipas, MD, is Principal Investigator.
About Pancreatic Cancer
The American Cancer Society estimates that 37,680 Americans will be diagnosed with pancreatic cancer, and 34,290 in the US will die of the disease in 2008, making pancreatic cancer the fourth leading cause of cancer death overall. The incidence of diagnosis peaks in the sixth and seventh decade of life. Because early symptoms such as anorexia, weight loss, weakness, fatigue, abdominal pain, and nausea are nonspecific, the diagnosis is often delayed for many patients. Consequently, more than 80% of patients present with locally advanced (unresectable) or metastatic disease. Patients with locally advanced disease have a median survival of 6 to 10 months despite systemic therapy, and patients with metastatic disease at initial diagnosis have a median survival of 3 to 6 months. Currently, the most widely used chemotherapeutic regimens involve gemcitabine either alone or in combination with other agents such as erlotinib, 5-FU, cisplatin, docetaxel, or irinotecan.
About CTGF and Pancreatic Cancer
Research has shown that the CTGF gene is overexpressed in human pancreatic cancer. One study found that among pancreatic cancer tissue samples taken from 19 patients, 15 exhibited an average 59-fold enhancement of CTGF gene expression over normal pancreatic tissue compared to an average 4.5-fold increase above normal in chronic pancreatitis, a disease where CTGF over-expression is associated with pancreatic fibrosis1.
CTGF was identified as an invasion-specific gene in pancreatic ductal adenocarcinoma (PDAC)2 and is highly expressed within the neoplastic epithelium3. The CTGF polypeptide is expressed and secreted by PDAC tumor cells and stromal cells, including stellate cells, and may have both autocrine and paracrine effects on these cell types.
CTGF has been shown to be involved in tumor growth and metastasis4,5. A direct effect of CTGF on pancreatic tumor growth was demonstrated in a study in which over-expression of CTGF in human pancreatic cancer cells enhanced tumor formation in animals as well as their ability to proliferate in cell culture independent of cell anchorage, a hallmark of cancer cell growth4.
In addition, PDAC tumors often exhibit a high degree of desmoplasia, characterized by a fibrotic connective tissue stroma, the extent of which has been found to correlate with CTGF levels1. CTGF has been shown to promote epithelial to mesenchymal transition (EMT)6, a process whereby normal epithelial cells become migratory, matrix-producing fibroblasts, which has been shown to be important during invasion and metastasis7.
Anti-CTGF Therapy for Pancreatic Cancer FG-3019 selectively binds to and blocks the action of CTGF. A potential role for anti-CTGF therapy in treating pancreatic cancer is supported by studies in animal models demonstrating that FG-3019 can inhibit the growth of human pancreatic tumors cells and prevent metastasis4,5.
Other Clinical Programs with FG-3019
FibroGen has completed phase 1 studies of FG-3019 in patients with idiopathic pulmonary fibrosis and diabetic kidney disease (microalbuminuria). Current Phase 1b studies are evaluating FG-3019 in diabetic kidney disease (macroalbuminuria) and steroid-resistant focal segmental glomerulosclerosis (FSGS).
To date, FG-3019 has been well tolerated in all patient populations tested.
About FibroGen
FibroGen, Inc. is a biotechnology-based drug discovery company using its expertise in the fields of tissue fibrosis, CTGF, and hypoxia-inducible factor (HIF) biology to discover, develop, and commercialize novel therapeutics for fibrotic disorders, diabetic complications, anemia, conditions associated with tissue damage or injury, cancer, and other areas of unmet medical need. FibroGen also develops and produces recombinant human collagens and gelatins using unique production technology that provides the basis for FibroGen’s proprietary cosmetic dermal filler and biomaterials supply business.
References:
1. Wenger C, et al. Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells. Oncogene 1999; 18:1073-1080.
2. Ryu B, et al. Invasion-specific genes in malignancy: serial analysis of gene expression comparisons of primary and passaged cancers. Cancer Res. 2001; 61:1833-1838.
3. Iacobuzio-Donahue CA, et al. Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasion. Am J Pathol. 2002 Jan;160(1):91-9.
4. Dornhöfer N, et al. Connective tissue growth factor specific mAb therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 2006; 66:5817-27.
5. Aikawa T, et al. Connective tissue growth factor specific antibody attenuates tumor growth, metastasis and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol. Cancer Ther. 2006 May;5(5):1108-16.
6. Burns WC, et al. Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition: implications for diabetic renal disease. J Am Soc Nephrol. 2006 Sep;17(9):2484-94.
7. Yang J and Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008 Jun;14(6):818-29.
SOURCE: FibroGen, Inc.
Post Views: 590
FibroGen today announced that an open-label, phase 1 clinical trial designed to evaluate the safety and tolerability of FG-3019 in combination with gemcitabine and erlotinib in patients with locally advanced or metastatic pancreatic cancer has commenced
San Francisco, CA, USA | December 15, 2008 | FibroGen, Inc. today announced that an open-label, phase 1 clinical trial designed to evaluate the safety and tolerability of FG-3019, a fully human monoclonal antibody against connective tissue growth factor (CTGF), in combination with gemcitabine and erlotinib in patients with locally advanced or metastatic pancreatic cancer has commenced.
The study is an open-label, dose-escalation trial expected to enroll up to 18 patients and to test three dose levels of FG-3019 administered via infusion every two weeks. After the second administration of FG-3019, patients will initiate treatment with gemcitabine (Gemzar®) and erlotinib (Tarceva®). Patients will continue on FG-3019 treatment until disease progression as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary objectives of the study are to evaluate the activity and pharmacokinetics of FG-3019 in combination with gemcitabine and erlotinib.
The study is being conducted at two sites: at Stanford University School of Medicine, Stanford, CA, where Albert C. Koong, MD, Ph.D., is Principal Investigator and at Dartmouth Hitchcock Medical Center, Lebanon, NH, where Marc J. Pipas, MD, is Principal Investigator.
About Pancreatic Cancer
The American Cancer Society estimates that 37,680 Americans will be diagnosed with pancreatic cancer, and 34,290 in the US will die of the disease in 2008, making pancreatic cancer the fourth leading cause of cancer death overall. The incidence of diagnosis peaks in the sixth and seventh decade of life. Because early symptoms such as anorexia, weight loss, weakness, fatigue, abdominal pain, and nausea are nonspecific, the diagnosis is often delayed for many patients. Consequently, more than 80% of patients present with locally advanced (unresectable) or metastatic disease. Patients with locally advanced disease have a median survival of 6 to 10 months despite systemic therapy, and patients with metastatic disease at initial diagnosis have a median survival of 3 to 6 months. Currently, the most widely used chemotherapeutic regimens involve gemcitabine either alone or in combination with other agents such as erlotinib, 5-FU, cisplatin, docetaxel, or irinotecan.
About CTGF and Pancreatic Cancer
Research has shown that the CTGF gene is overexpressed in human pancreatic cancer. One study found that among pancreatic cancer tissue samples taken from 19 patients, 15 exhibited an average 59-fold enhancement of CTGF gene expression over normal pancreatic tissue compared to an average 4.5-fold increase above normal in chronic pancreatitis, a disease where CTGF over-expression is associated with pancreatic fibrosis1.
CTGF was identified as an invasion-specific gene in pancreatic ductal adenocarcinoma (PDAC)2 and is highly expressed within the neoplastic epithelium3. The CTGF polypeptide is expressed and secreted by PDAC tumor cells and stromal cells, including stellate cells, and may have both autocrine and paracrine effects on these cell types.
CTGF has been shown to be involved in tumor growth and metastasis4,5. A direct effect of CTGF on pancreatic tumor growth was demonstrated in a study in which over-expression of CTGF in human pancreatic cancer cells enhanced tumor formation in animals as well as their ability to proliferate in cell culture independent of cell anchorage, a hallmark of cancer cell growth4.
In addition, PDAC tumors often exhibit a high degree of desmoplasia, characterized by a fibrotic connective tissue stroma, the extent of which has been found to correlate with CTGF levels1. CTGF has been shown to promote epithelial to mesenchymal transition (EMT)6, a process whereby normal epithelial cells become migratory, matrix-producing fibroblasts, which has been shown to be important during invasion and metastasis7.
Anti-CTGF Therapy for Pancreatic Cancer FG-3019 selectively binds to and blocks the action of CTGF. A potential role for anti-CTGF therapy in treating pancreatic cancer is supported by studies in animal models demonstrating that FG-3019 can inhibit the growth of human pancreatic tumors cells and prevent metastasis4,5.
Other Clinical Programs with FG-3019
FibroGen has completed phase 1 studies of FG-3019 in patients with idiopathic pulmonary fibrosis and diabetic kidney disease (microalbuminuria). Current Phase 1b studies are evaluating FG-3019 in diabetic kidney disease (macroalbuminuria) and steroid-resistant focal segmental glomerulosclerosis (FSGS).
To date, FG-3019 has been well tolerated in all patient populations tested.
About FibroGen
FibroGen, Inc. is a biotechnology-based drug discovery company using its expertise in the fields of tissue fibrosis, CTGF, and hypoxia-inducible factor (HIF) biology to discover, develop, and commercialize novel therapeutics for fibrotic disorders, diabetic complications, anemia, conditions associated with tissue damage or injury, cancer, and other areas of unmet medical need. FibroGen also develops and produces recombinant human collagens and gelatins using unique production technology that provides the basis for FibroGen’s proprietary cosmetic dermal filler and biomaterials supply business.
References:
1. Wenger C, et al. Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells. Oncogene 1999; 18:1073-1080.
2. Ryu B, et al. Invasion-specific genes in malignancy: serial analysis of gene expression comparisons of primary and passaged cancers. Cancer Res. 2001; 61:1833-1838.
3. Iacobuzio-Donahue CA, et al. Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasion. Am J Pathol. 2002 Jan;160(1):91-9.
4. Dornhöfer N, et al. Connective tissue growth factor specific mAb therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 2006; 66:5817-27.
5. Aikawa T, et al. Connective tissue growth factor specific antibody attenuates tumor growth, metastasis and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol. Cancer Ther. 2006 May;5(5):1108-16.
6. Burns WC, et al. Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition: implications for diabetic renal disease. J Am Soc Nephrol. 2006 Sep;17(9):2484-94.
7. Yang J and Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008 Jun;14(6):818-29.
SOURCE: FibroGen, Inc.
Post Views: 590
