FGFR2b protein overexpression is an emerging biomarker and potential therapeutic target in advanced gastric and gastroesophageal junction cancers. However, reliable global prevalence data have been limited, especially using centralized testing and a validated immunohistochemistry assay.
A pooled analysis published in ESMO Open evaluated the prevalence of FGFR2b protein overexpression in tumor samples collected during prescreening for two global phase 3 bemarituzumab studies: FORTITUDE-101 and FORTITUDE-102.
The original article, titled “Global prevalence of FGFR2b protein overexpression in advanced gastric cancer and gastroesophageal junction cancers: pooled analysis of two bemarituzumab phase III studies,” was published in ESMO Open, Volume 11, Issue 6, in June 2026.
Authors: S.B. Maron, R.-H. Xu, Z.A. Wainberg, S.Y. Rha, Y. Zhang, F. Pietrantonio, S.C.S. Oliveira, Y. Li, M.-H. Chen, K. Korphaisarn, E. Elimova, C.A. Calderon, F.V. Herpe, W.P. Yong, T.M. Dos Santos, M. Tan, K. Isse, R.E. Yanes, and K. Shitara.
What Is Bemarituzumab?
Bemarituzumab is a humanized monoclonal antibody selective for FGFR2b, the IIIb splice isoform of FGFR2.
It acts through two mechanisms: blocking ligand binding to FGFR2b and inhibiting downstream signaling pathways involved in tumor growth, while its afucosylated Fc structure enhances antibody-dependent cellular cytotoxicity against FGFR2b-expressing tumor cells.
Through this mechanism, bemarituzumab is being developed as a biomarker-directed therapy for FGFR2b-overexpressing gastric and gastroesophageal junction cancers.
Read more about Bemarituzumab: Uses in Cancer, Side Effects, Dosages, Expectations on OncoDaily.
Study Design
This pooled analysis included tumor samples from patients prescreened for enrollment in the global phase 3 FORTITUDE-101 and FORTITUDE-102 trials.
Both studies were randomized, double-blind, placebo-controlled phase 3 trials conducted in the first-line setting for patients with unresectable, locally advanced, or metastatic gastric or gastroesophageal junction adenocarcinoma.
FORTITUDE-101 was designed to evaluate bemarituzumab plus mFOLFOX6 versus placebo plus mFOLFOX6. FORTITUDE-102 evaluated bemarituzumab plus chemotherapy plus nivolumab versus placebo plus chemotherapy plus nivolumab. In FORTITUDE-102, chemotherapy consisted of either mFOLFOX6 or capecitabine and oxaliplatin, selected by the investigator before randomization.
As of the data cutoff on February 20, 2025, a total of 7,910 tumor samples had evaluable FGFR2b immunohistochemistry results: 3,752 from FORTITUDE-101 and 4,158 from FORTITUDE-102.
FGFR2b protein overexpression was assessed centrally by immunohistochemistry using the investigational VENTANA FGFR2b (FPR2-D) RxDx Assay.
Two cutoffs were evaluated: FGFR2b any 2+/3+, defined as any percentage of tumor cells with moderate or strong membrane staining, and FGFR2b ≥10% 2+/3+, defined as at least 10% of tumor cells with moderate or strong membrane staining.
Patient and Sample Characteristics
Among the 7,910 evaluable samples, 67.8% were from male patients. More than half of the population was from the Asia-Pacific region, including Mainland China, followed by Europe, the Middle East, and Africa.
Most tumor samples were collected from the primary tumor site, and the majority were biopsy specimens. Overall, 71.1% of samples were from gastric cancer, 15.5% from gastroesophageal junction cancer, and 13.4% had an unspecified gastric or gastroesophageal junction primary tumor location.
Key Findings
In the pooled population, 36.5% of tumor samples showed FGFR2b any 2+/3+ protein overexpression. This corresponded to 2,887 of 7,910 evaluable samples.
Using the higher cutoff, 16.6% of tumor samples showed FGFR2b ≥10% 2+/3+ overexpression. This corresponded to 1,310 of 7,910 evaluable samples. Among tumors positive for FGFR2b any 2+/3+, 45.4% also met the FGFR2b ≥10% 2+/3+ threshold.
Prevalence estimates were consistent across the two phase 3 prescreening populations. FGFR2b any 2+/3+ was observed in 37.3% of samples from FORTITUDE-101, 35.8% of samples from FORTITUDE-102, and 36.5% of samples in the pooled analysis. In FORTITUDE-102 alone, FGFR2b ≥10% 2+/3+ was observed in 17.3% of samples.
FGFR2b prevalence was generally consistent across patient and sample subgroups, including age, sex, biopsy versus resection samples, primary versus metastatic collection site, primary tumor location, and geographic region.
Read more about FORTITUDE-101 Trial from ESMO 2025 on OncoDaily.
Clinical Context
Data from the phase 2 FIGHT study informed the design of the phase 3 FORTITUDE-101 and FORTITUDE-102 studies. In FIGHT, enhanced benefit was reported in patients with FGFR2b ≥10% 2+/3+ tumors.
The current pooled analysis does not report treatment outcomes, but it provides large-scale prevalence data from the prescreening programs of two phase 3 bemarituzumab trials. The study also noted that FGFR2b expression can be heterogeneous, with variability in both staining intensity and the percentage of tumor cells showing membrane staining.
Takeaway
This pooled analysis represents the largest global assessment to date of FGFR2b protein overexpression in advanced gastric and gastroesophageal junction cancers using centralized immunohistochemistry testing.
FGFR2b overexpression was identified in a meaningful proportion of patients, with 36.5% of evaluable tumors showing any moderate-to-strong FGFR2b membrane staining and 16.6% meeting the ≥10% 2+/3+ threshold.
These findings help define how often FGFR2b overexpression is seen in advanced gastric and gastroesophageal junction cancers and may support future biomarker-directed treatment strategies.