Lancet Oncol: Bemarituzumab combined with mFOLFOX6 is promising for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma

Patients with HER2-negative advanced gastric or gastric-oesophageal junction adenocarcinoma have a poor
prognosis.
Bemarituzumab is an innovative, humanized isoform-selective monoclonal antibody targeting the FGF family FGFR2b, which blocks ligand signaling binding of FGF and activates FGFR2b, inhibiting multiple downstream pathways and thereby inhibiting cancer growth
.

To evaluate the efficacy and safety
of Bemarituzumab in combination with a modified 5-fluorouracil, folic acid, and oxaliplatin (mFOLFOX6) regimen in patients with gastric or gastroesophageal junction adenocarcinoma selected for FGFR2b.

This is a randomized, double-blind, placebo-controlled phase 2 trial (FIGHT) that recruited patients aged 18 years and older with HER2-positive, FGFR2b-selected gastric or gastric-oesophageal junction adenocarcinoma from 17 countries and excluded patients
who had previously received selective inhibitors of the FGF-FGFR pathway.
Patients were randomized (1:1) to receive either Bemarituzumab + mFOLFOX6 or placebo + mFOLFOX6
.
The primary endpoint was progression-free survival
.

A total of 910 patients were screened from 14 November 2017 to 8 May 2020, of whom 155 were randomized to Bemarituzumab (n=77) or placebo (n=78).

The median age of the patients was 60.
0 years, 44 (28%) were female, 89 (57%) were Asian, and 61 (39%) were Caucasian
.
At a median follow-up of 10.
9 months, median progression-free survival in the Bemarituzumab and placebo groups was 9.
5 months and 7.
4 months, respectively (HR 0.
68, p=0.
073).

Common grade 3 and above adverse effects were decreased neutrophil counts (Bemarituzumab versus placebo: 30 versus 35 percent), corneal disease (24 versus 0), neutropenia (13 versus 9 percent), stomatitis (9 versus 1 percent), and anemia (8 versus 13 percent).

The incidence of serious treatment-related adverse reactions in the Bemarituzumab and placebo groups was 32% and 36%,
respectively.
Nine (12%) and 15 (19%) patients in the Bemarituzumab and placebo groups, respectively, experienced serious mFOLFOX6-related adverse effects
.
Three treatment-related deaths occurred in the Bemarituzumab group (two from sepsis and one from pneumonia) and no treatment-related deaths
in the placebo group.

In summary, although there was no statistically significant difference in progression-free survival, Bemarituzumab therapy showed promising clinical efficacy
in patients with HER2-negative advanced gastric or gastric-oesophageal junction adenocarcinoma.
A related Phase 3 clinical trial is ongoing
.

Original source:

Zev A Wainberg, et al.
Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study.
The Lancet Oncology.
October 13, 2022.
https://doi.
org/10.
1016/S1470-2045(22)00603-9