SOUTH SAN FRANCISCO, Calif.—Five Prime Therapeutics, Inc. reported today the publication of results from the Phase 1 escalation and expansion study of bemarituzumab in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma (GEA) in the digital edition of the Journal of Clinical Oncology.
Bemarituzumab (anti-FGFR2b) is a first-in-class isoform-selective antibody with enhanced antibody-dependent cell-mediated cytotoxicity. The therapy is in development as a targeted immunotherapy for tumors that overexpress FGFR2b.
“Monotherapy activity of bemarituzumab and its lack of significant overlapping toxicities with standard chemotherapeutic agents suggest that combining bemarituzumab with chemotherapy may potentially benefit patients in the front-line setting whose GEA tumors overexpress FGFR2b,” said Daniel Catenacci, M.D., associate professor at the University of Chicago Medical Center and Biological Sciences.
The purpose of the Phase 1 trial was to evaluate the safety, pharmacokinetics and preliminary activity of bemarituzumab in patients with FGFR2b-overexpressing GEA. 79 patients were enrolled in the trial, and there were no dose-limiting toxicities reported. Bemarituzumab was well tolerated; the most frequent treatment-related adverse events (TRAEs) were fatigue, nausea and dry eye. The overall response rate observed in this study of advanced-stage patients with high FGFR2b-overexpressing GEA was 17.9%. Five of the 28 patients with high FGFR2b expression achieved a confirmed partial response.
“Fifty-two (92.9%) of 56 patients with GEA enrolled across the study (parts 1a and 1b combined) were efficacy evaluable per protocol, and all received a dose of at least 6 mg/kg every 2 weeks. Twenty-eight of these patients had tumors that had high FGFR2b overexpression (all FGFR2 amplified by FISH [fluorescence in situ hybridization]), 4 patients had tumors with moderate expression, 12 patients had tumors with low expression, and 8 patients had tumors with no or unknown expression,” the article notes. “All tumors with moderate, low, or no or unknown FGFR2b expression were nonamplified by FISH.”
“The ORR [overall response rate] was 17.9% (95% CI, 6.1% to 36.9%) in patients with GEA with high FGFR2b overexpression, with a median DOR [duration of response] of 12.6 weeks (range, 9.1-19.1 weeks). Stable disease was the best observed response in 13 additional patients, leading to an overall DCR [disease control rate] (PR [partial response] plus stable disease) of 64.3% (95% CI, 44.1% to 81.4%) in the subgroup with high FGFR2b overexpression. In the 12 patients with GEA with low FGFR2b overexpression, there was 1 confirmed response (ORR, 8.3%; 95% CI, 0.2% to 38.5%), with a DOR of 18.1 weeks,” continues the article. “The blood from this patient with tumor response tested negative for FGFR2 circulating tumor DNA amplification. There were no responses in the subgroups with moderate (n = 4) and no or unknown (n = 10) FGFR2b overexpression.”
The article also points out that “reversible TRAEs of grade 2 symptomatic corneal events, which required intervention and in one case drug discontinuation, were reported in 3 (10.7%) of 28 patients who were treated with a dose of ≥ 10 mg/kg for ≥ 70 days. An analysis of PK parameters did not identify a clear association between Cmax [Maximum concentration], Ctrough [trough concentration], or AUC [area under the curve] for corneal events; however, the small number of patients limits definitive conclusions.The mechanism of the corneal toxicity is hypothesized to be a result of inhibition of FGF10, 1 of the 3 growth factors inhibited by bemarituzumab, and involved in the regulation of corneal epithelial wound healing.”
Bemarituzumab is also being evaluated in combination with mFOLFOX6 in the Phase 3 FIGHT (FGFR2b Inhibition in Gastric and Gastroesophageal Junction Cancer Treatment) trial in a front-line treatment setting.
“Gastroesophageal adenocarcinoma is the third most common cause of cancer death worldwide and the median overall survival of patients who present with advanced disease remains dismal at only 11 months,” said Helen Collins, M.D., executive vice president and chief medical officer of Five Prime Therapeutics. “The results of this study underscore the potential of bemarituzumab evaluation as a novel treatment option for patients with advanced gastric and gastroesophageal junction cancer.”