Date: 2017-02-03
Type of information: Publication of results in a medical journal
phase: 1-2
Announcement: publication of results in the Journal of Cancer Clinical Trials
Company: FibroGen (USA - CA)
Product: pamrevlumab (FG-3019)
Action
mechanism: monoclonal antibody. FG-3019 is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. FibroGen is currently conducting clinical studies of FG-3019 in idiopathic pulmonary fibrosis, pancreatic cancer, and Duchenne muscular dystrophy. While the safety and efficacy of FG-3019 have not been established, it has been well tolerated to date, with no apparent safety signals in ten Phase 1 and Phase 2 clinical studies and more than 350 treated patients to date. In desmoplastic, or fibrotic, cancers such as pancreatic cancer, CTGF in the extensive fibrous stroma associated with the tumor promotes abnormal proliferation of stromal cells and tumor cells, induces extracellular-matrix, or ECM, deposition that provides a substrate for tumor cell adherence, promotes angiogenesis, and promotes metastasis by enhancing cell motility, invasion, and survival. Studies in a transgenic mouse model of pancreatic cancer indicate that treatment with FG-3019 in combination with chemotherapy may enhance the efficacy of chemotherapy and improve survival.
Disease: pancreatic ductal adenocarcinoma
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On February 3, 2017, FibroGen announced that clinical results from the company’s open-label, dose-escalation Phase 1/2 study (FGCL-MC3019-028) of pamrevlumab in pancreatic cancer were published in the Journal of Cancer Clinical Trials (Picozzi et al., J Cancer Clin Trials 2017, 2:123). The published results support a dose-related increase in survival in advanced pancreatic cancer, and that pamrevlumab can be safely combined with chemotherapy. In the 028 trial, the safety and efficacy of increasing doses of pamrevlumab were evaluated in combination with two chemotherapy agents, gemcitabine and erlotinib, in 75 patients with previously untreated Stage III or Stage IV pancreatic ductal adenocarcinoma. Pamrevlumab was well tolerated with no dose-limiting toxicity observed and no dose-related trends observed in type or incidence of serious adverse events. Toxicity, tumor response by CA19-9 and CT scan-based RECIST criteria, progression-free survival (PFS) and overall survival (OS) were assessed. In a post-hoc analysis, FG-3019 trough plasma levels (a measure of exposure) on Day 15 (D15Cmin) and baseline CTGF levels were correlated with clinical outcomes. High FG-3019 exposure (D15 Cmin ?150 ?g/mL) was associated with improved median OS (9.0 vs 4.4 months, (D15 Cmin <150 ?g/mL), p=0.024), and one-year OS rate (34.2% vs. 10.8%, respectively, p=0.026), respectively. Plasma CTGF showed potential as a prognostic biomarker, as low baseline CTGF levels (<10 ng/mL) were associated with improved OS (10.1 vs 4.4 months (?10 ng/mL), p=0.028).
