FibroGen FG-3019 reports the results of the Phase 2 study for the treatment of pancreatic cancer -
FibroGen, Inc. (FibroGen ) today announced the results of a Phase 2 study of open study of FG-3019, an investigational anti-fibrotic antibody, in combination with erlotinib and gemcitabine for the treatment of patients with ductal adenocarcinoma of the pancreas locally advanced or metastatic (PDAC). In the study, FG-3019 has demonstrated an improvement in dose-dependent and one year overall survival rate, and appeared to be safe and well tolerated. Full data will be presented today at the 2014 American Society of Clinical Oncology (ASCO) annual meeting in a poster session 08: 00 to 11:45 CDT, Place S Hall A2, Abstract number 4138.
the phase 2 study is an open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and FG-3019 capacity to improve outcomes for patients with pancreatic cancer treated with chemotherapy. Sixty-five patients were included in the study, 66 (88%) with stage 4 metastatic disease. The study evaluated FG-3019 3 mg / kg, 10 mg / kg, 15 mg / kg, 25 mg / kg, 35 mg / kg and 45 mg / kg administered every two weeks, and FG doses -3019 17.5 mg / kg and 22.5 mg / kg administered weekly after a double loading dose. On Day 15, the treatment began with gemcitabine 1000 mg / m 2 twice weekly for three out of four weeks and erlotinib 100 mg per day. Treatment continued until progression of the cancer or the patient is removed for other reasons. Patients were then followed until death. the status of the tumor was assessed by CT imaging every eight weeks to assess changes in tumor mass.
The study demonstrated an increase in dose-related survival. At the lowest dose, no patients survived for a year, while in the highest doses approximately 30% of patients survived one year. The results showed a significant relationship between patient survival and minimum plasma concentrations of FG-3019 (C min) measured immediately before the second drug dose at day 15. Cmin higher or equal to 150 pg / mL was associated with free survival significantly improved progression>
most adverse events in the study were mild to moderate and were consistent with those observed for erlotinib plus gemcitabine treatment without FG-3019. No pattern of dose-dependent trend was identified, and higher doses of FG-3019 was not associated with a higher number or a greater severity of SAE. FG-3019 treatment was associated with improvement of no apparent increase in the survival of the toxicity of chemotherapy, suggesting that FG-3019 could provide an effective complement to other chemotherapy regimens.
FibroGen plans to open a randomized phase 2 FG-3019 combined trial with gemcitabine plus nab-paclitaxel chemotherapy compared to chemotherapy alone in patients with a slightly inoperable pancreatic cancer that has not been treated before. The overall objective of the trial is to determine if FG-3019 in combination with other treatments can convert inoperable pancreatic cancer in operable cancer. removal of the tumor is usually the only chance for cure of pancreatic cancer, but only 20% of patients are eligible for surgery.
The FG-3019 Preclinical studies for pancreatic cancer
FG-3019 has demonstrated a reduction in tumor mass and metastasis in several models murine pancreatic cancer, including transgenic mouse model CPK. KPC mice spontaneously develop pancreatic cancer that closely approximates many characteristics of the human disease, including genetic mutations like the expression of CTGF, wide stroma, metastases and ascites, or abdominal fluid, training. KPC mouse tumors, such as human pancreatic cancer tumors, are highly resistant to anti-cancer therapies. FG-3019 plus gemcitabine mice more than doubled survival time treated with chemotherapy alone. FG-3019 inhibits the expression of XIAP, one of a family of proteins whose function is to inhibit apoptosis. High expression of XIAP protein promotes cell survival and is a mechanism by which tumor cells can become resistant to chemotherapeutic agents. FG-3019 significantly decreased XIAP levels whereas gemcitabine did not, and the combination of FG-3019 and gemcitabine is more effective. In both the study of mouse and KPC in this clinical trial, the FG-3019 treatment had a significant effect on survival without any apparent increase in toxicity of the chemotherapeutic treatment.
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