In a phase I trial reported in the Journal of Clinical Oncology, Daniel V.T. Catenacci, MD, PhD, and colleagues found that the first-in-class anti–fibroblast growth factor receptor 2b (FGFR2b) antibody bemarituzumab showed activity in patients with high FGFR2b-overexpressing, advanced-stage gastroesophageal adenocarcinoma.
Daniel V.T. Catenacci, MD, PhD
The multicountry, multicenter study enrolled a total of 79 patients. The population included two dose-escalation cohorts, including 19 patients with recurrent solid tumors receiving doses of bemarituzumab ranging from 0.3 to 15 mg/kg every 2 weeks and 8 patients with advanced-stage gastroesophageal adenocarcinoma receiving doses of bemarituzumab ranging from 3 to 10 mg/kg every 2 weeks. A dose-expansion cohort consisted of 45 patients with advanced-stage FGFR2b-overexpressing gastroesophageal adenocarcinoma at levels of no to high overexpression, as well as 7 patients with FGFR2b-overexpressing advanced bladder cancer. A total of 58% of patents were Asian and 40% were white. Patients had received a median of three prior therapies. Efficacy was assessed in 52 evaluable patients with gastroesophageal adenocarcinoma and 6 with bladder cancer.
No dose-limiting toxicities were reported and the recommended dose for the dose-expansion cohort was identified as 15 mg/kg every 2 weeks.
Among all patients, the most common treatment-related adverse events of any grade were fatigue (18%), nausea (11%), and dry eyes (10%). Grade 3 or 4 adverse events occurred in 40 (56%) of patients and were considered treatment-related in 6 (all grade 3; nausea in 2 and anemia, neutropenia, increased aspartate transaminase, increased alkaline phosphatase, vomiting, and infusion reaction in 1 each). Reversible grade 2 corneal treatment-related adverse events occurred in 3 of 28 patients receiving a dose of ≥ 10 mg/kg.
Among the 52 evaluable patients with gastroesophageal adenocarcinoma (of whom all received a dose of ≥ 6 mg/kg every 2 weeks), partial response was observed in 5 (17.9%) of 28 with high FGFR2b-overexpression, with a median duration of response of 12.6 weeks. Stable disease was observed in 13 additional patients, yielding an overall disease control rate of 64.3%. Partial response was observed in 1 (8.3%) of 12 patients with gastroesophageal adenocarcinoma with low FGFR2b overexpression; no responses were observed in 4 patients with moderate overexpression or 10 with unknown overexpression. No responses were observed among five patients with bladder cancer with high overexpression or one with low overexpression.
The investigators concluded, “Overall, bemarituzumab seems to be well tolerated and demonstrated single-agent activity as late-line therapy in patients with advanced-stage gastroesophageal adenocarcinoma. Bemarituzumab is currently being evaluated in combination with chemotherapy in a phase III trial as front-line therapy for patients with high FGFR2b-overexpressing advanced-stage gastroesophageal adenocarcinoma.”
Dr. Catenacci, of the University of Chicago, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.