Bemarituzumab is an investigational, potential first-in-class targeted antibody designed to block specific fibroblast growth factors from binding and activating FGFR2b.
Treatment with bemarituzumab in combination with chemotherapy was found to improve overall survival (OS) in patients with FGFR2b-positive, human epidermal growth factor receptor 2 (HER2)-negative frontline advanced gastric or gastroesophageal junction cancers (GEJ). The results of the phase 2 FIGHT trial were presented during a presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
Bemarituzumab (anti-FGFR2b) is an investigational, potential first-in-class targeted antibody designed to block specific fibroblast growth factors (FGFs) from binding and activating FGFR2b, thereby inhibiting downstream pro-tumor signaling pathways and possibly limiting cancer progression. The new trial data include median OS, a secondary endpoint achieved with longer follow-up and additional analyses of patient subgroups.
"Gastric cancer is the fourth leading cause of cancer death globally and 30% of frontline HER2-negative gastric cancer patients have tumors that overexpress FGFR2b," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release. "These updated results underscore the benefits that bemarituzumab plus chemotherapy may bring to patients who have been fighting this aggressive disease with chemotherapy alone. We now look forward to advancing bemarituzumab into phase 3 development."
After a median follow-up of 12.5 months, bemarituzumab added to chemotherapy among all randomized patients showed a median OS of 19.2 months compared with 13.5 months for chemotherapy alone (n=155, HR: 0.6; 95% CI: 0.38, 0.94). Further, an exploratory pre-specified subgroup analysis showed that in patients with >10% of tumor cells overexpressing FGFR2b by immunohistochemistry, median OS was 25.4 months with bemarituzumab compared with 11.1 months (n=96, HR: 0.41; 95% CI: 0.23, 0.74) in the chemotherapy only group.
The incidence of all grade adverse events (AEs) was 100% in the bemarituzumab plus chemotherapy group compared with 98.7% in the chemotherapy only cohort. The incidence of corneal AEs was 67.1% in the bemarituzumab plus chemotherapy cohort compared with 10.4% in the chemotherapy group. The most common corneal AE was found to be dry eye, which was reported in 26.3% of patients; however, the majority of corneal AEs were reversible, according to the study.
The FDA granted bemarituzumab with Breakthrough Therapy Designation in April 2021 based on a subset of patients from the FIGHT trial who showed at least 10% of tumor cells overexpressing FGFR2b.
"These updated results further validate our work on the role of FGFR2b overexpression in gastroesophageal cancer and demonstrate that treatment with bemarituzumab in combination with chemotherapy can deliver a clinically significant reduction in the risk of disease progression for patients whose tumors overexpress FGFR2b," said Daniel V.T. Catenacci, MD, PhD, medical oncologist and principal investigator at the University of Chicago, in a press release.