Date: 2016-01-27
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 2016 American Society of Clinical Oncology (ASCO) GastroIntestinal Cancer
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: unresectable pancreatic cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This phase 1/2 trial to evaluate the safety, tolerability and efficacy of FG-3019 administered with gemcitabine and Nab-paclitaxel in the treatment of locally advanced, unresectable pancreatic cancer. In this study, patients with inoperable locally advanced pancreatic cancer, assessed by CT scans, are carefully staged with PET scans, endoscopic tissue biopsies, and laparoscopy. Subjects are randomized to six cycles of chemotherapy with gemcitabine and nab-paclitaxel with or without FG-3019. (NCT02210559)
Latest
news: * On January 27, 2016, FibroGen announced early results from a Phase 2, randomized, open-label study of FG-3019 in combination with gemcitabine and nab-paclitaxel (chemotherapy) compared to those chemotherapy agents alone for the treatment of patients with locally advanced pancreatic ductal adenocarcinoma (PDAC) who have failed resection scoring and are characterized as inoperable. The tumors in 3 of the first 4 evaluable subjects randomized to FG-3019 plus chemotherapy were converted from inoperable to operable condition. In contrast, 1 of the first 4 evaluable subjects treated with chemotherapy alone was considered operable. Treatment with FG-3019 in combination with chemotherapy was generally well tolerated. There were no complications from laparoscopy or biopsies that were clinically significant or delayed dosing, and to date there have been no safety imbalances between treatment arms. The data were presented at the 2016 American Society of Clinical Oncology (ASCO) GastroIntestinal Cancer Meeting in a poster session on January 22, 2016 (Abstract 4138). The study is targeted to enroll a total of 42 subjects, so these data represent an early assessment. Twelve subjects out of the total target of 42 have been enrolled to date. Among the 6 randomized to FG-3019 plus chemotherapy, 2 are still on treatment, 1 discontinued treatment due to complications of chemotherapy and 3 completed treatment. Tumors in the 3 subjects who completed treatment were considered operable after treatment. Two subjects had complete tumor removal (R0) and one subject had microscopic tumor remaining after surgery (R1). Among the 6 subjects randomized to chemotherapy alone, 2 are still on treatment, 2 subjects discontinued treatment due to tumor progression during the course of the study, and two subjects completed treatment. Of the two subjects who completed treatment, one was considered to have operable cancer and had a complete tumor removal (R0). After 2 cycles of treatment in these first 12 subjects, plasma levels of CA19.9, a non-specific tumor marker, showed a mean reduction of 78.3% with FG-3019 plus chemotherapy compared to 48.7% with chemotherapy alone. An additional advantage of the study is that it will provide tumor biopsy samples with which we plan to assess changes in biomarkers of the tumor, stroma, and inflammatory cells. In a previous study, increasing doses of FG-3019 were combined with gemcitabine plus erlotinib for treatment of subjects with advanced pancreatic cancer. That study (N=75) indicated a dose-related increase in survival. At the lowest doses of FG-3019, no subjects survived for one year, while at the highest doses approximately 30% of subjects survived one year. The study further demonstrated a relationship between blood levels of FG-3019 and survival.
