Bemarituzumab Shows Promise For FGFR2b-Overexpressing GEA

Author: By Laura Cowen, medwireNews Reporter 

medwireNews: A phase I trial of bemarituzumab, a first-in-class immunoglobulin G1 monoclonal antibody against fibroblast growth factor receptor (FGFR)2b, has shown good tolerability and evidence of efficacy among some patients with advanced gastric and gastro-oesophageal junction adenocarcinoma (GEA) who overexpress the protein. 

The open-label, multicentre trial included two cohorts of patients with recurrent solid tumours (n=19), and recurrent or metastatic GEA (n=8), both of whom received intravenous bemarituzumab at a dose of 0.3–15.0 mg/kg every2 weeks.  

There were no dose-limiting toxicities and no maximum tolerated dose was identified in these groups, resulting in a recommended bemarituzumab dose of 15 mg/kg every 2 weeks 

A third dose-expansion cohort was then formed from 45 patients with advanced GEA with high, medium, low or no FGFR2b overexpression based on an immunohistochemistry assay, as well as an additional seven patients with FGFR2b-overexpressing advanced bladder cancer. 

Just over half (50.6%) of the 79 patients included in the study groups experienced any grade of treatment-related adverse event (TRAE), most commonly fatigue (17.7%), nausea (11.4%) and dry eye (10.1%). 

There were eight grade 3 TRAEs among six patients, including two cases of nausea and single cases of anaemia, neutropenia, increased aspartate amino transferase, increased alkaline phosphatase, vomiting, and an infusion reaction. 

There were also six serious TRAEs in five patients including three reversible grade 2 corneal TRAEs (ulcerative keratitis, limbal stem-cell deficiency, and corneal dystrophy) among 28 patients assigned to receive at least 10 mg/kg every 2 weeks for at least 70 days, one of which led to treatment discontinuation. 

In terms of efficacy, 17.9% of 28 patients with high FGFR2b-overexpressing GEA had a confirmed partial response, with a median response duration of 12.6 weeks. 

This “compares favorably with that of other noncytotoxic agents in GEA,” such as ramucirumab or checkpoint inhibitors, say Daniel Catenacci, from the University of Chicago in Illinois, USA, and co-investigators. 

Furthermore, an additional 13 patients experienced stable disease, resulting in an overall disease control rate of 64.3% in the subgroup with high FGFR2b overexpression. 

One (8.3%) patient with low FGFR2b overexpression also had a confirmed response but there were no responses in the subgroups with medium or no FGFR2b overexpression. Nor were there any responses among the six evaluable patients with bladder cancer. 

Writing in the Journal of Clinical Oncology, Daniel Catenacci et al conclude: “The monotherapy activity of bemarituzumab and its lack of significant overlapping toxicities with standard platinum and fluoropyrimidine chemotherapeutic agents suggest that combining bemarituzumab with chemotherapy may potentially benefit more patients in the front-line setting of FGFR2b-overexpressing GEA.” 

They add: “Early safety data suggest that bemarituzumab combined with oxaliplatin, fluorouracil, and leucovorin (mFOLFOX6) is tolerable in patients with advanced-stage [gastrointestinal] cancers, and a randomized, placebo-controlled, phase III study of mFOLFOX6 with bemarituzumab in patients with newly diagnosed advanced-stage GEA, the FIGHT trial, initiated enrolment in September 2018.” 

Reference 

Catenacci DVT, Rasco D, Lee J, et al. Phase I escalation and expansion study of bemarituzumab (FPA144) in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma. J Clin Oncol; Advance online publication 13 March 2020. doi: 10.1200/JCO.19.01834