Abstract 384P
Background
FGFR2 contributes to tumor progression by enhancing angiogenesis and proliferation. In the randomized FIGHT Phase 2 study, the FGFR2b splice isoform, also called IIIb, was overexpressed in ∼30% of gastric cancers that were not known to be HER2+. Adding bemarituzumab, a first-in-class, anti-FGFR2b monoclonal antibody to mFOLFOX6 improved outcomes, indicating FGFR2b as a promising therapeutic target. There is limited data on FGFR2b prevalence in other tumor types and we report here its expression in sqNSCLC and the overlap with programmed death-ligand 1 (PD-L1).
Methods
FGFR2b protein expression was determined using the VENTANA FGFR2b (FPR2-D) Assay, an automated immunohistochemistry (IHC) test specific for the “IIIb” isoform of the FGFR2 protein. Percentages of membranous tumor cell staining at each intensity (0 to 3+) were estimated by board-certified pathologists. A sample is considered to exhibit FGFR2b overexpression and is deemed positive when any moderate (2+) or strong (3+) membrane staining in tumor cells is detected. PD-L1 expression was assessed by IHC using the 22C3 antibody clone. All procured human specimens were collected under IRB approval with appropriate consent in compliance with all applicable regulations.
Results
250 samples were collected from patients with stage III and IV sqNSCLC (median age of 64 years) located in Asia, North/South America, and Europe. FGFR2b prevalence (any 2+/3+) in sqNSCLC was 20.8% (52/250) (95% Cl 15.8-25.8). The majority of cases (44/52) that exhibited FGFR2b overexpression demonstrated 2+, but not 3+ staining intensity. All cases (8/52) that were 3+ also had 2+ staining intensity. FGFR2b overlap with PD-L1 is shown in the table. Table: 384P
Prevalence in sqNSCLC samples (n=250) | ||
# of Positive Cases | % (95% CI) | |
FGFR2b (any 2+/3+) | 52 | 20.8 (15.8 - 25.8) |
Overlap of FGFR2b and PD-L1 | ||
FGFR2b (any 2+/3+) and PD-L1 (TPS <1%) | 24 | 9.6 (5.9 - 13.3) |
FGFR2b (any 2+/3+) and PD-L1 (TPS 1-49%) | 23 | 9.2 (5.6 - 12.8) |
FGFR2b (any 2+/3+) and PD-L1 (TPS ≥50%) | 5 | 2.0 (0.3 - 3.7) |
TPS, tumor proportion score.
Conclusions
Over 20% of sqNSCLC tissue samples overexpress FGFR2b, making it a promising therapeutic target for agents such as bemarituzumab.
Clinical trial identification
Editorial acknowledgement
Medical writing assistance was provided by Sahishnu Patel, an employee of Amgen Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
H. Akamatsu: Financial Interests, Personal, Other, honoraria and lecture fees: AstraZeneca, Eli Lilly and Company, Chugai Pharmaceutical Co., Pfizer, Taiho Pharmaceutical Co., Nippon Boehringer Ingelheim, Novartis Pharmaceuticals. J.C. Yang: Financial Interests, Personal, Other, honoraria: Boehringer Ingelheim, Roche, Chugai Pharma, MSD Oncology, AstraZeneca; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Novartis, AstraZeneca, Genentech, Clovis Oncology, Eli Lilly, MSD Oncology, Merck Serono, Celgene, Astellas Pharma, Bayer AG, Pfizer, Ono Pharmaceutical, Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim, AstraZeneca. K. WAKUDA: Financial Interests, Personal, Research Grant: Chugai Pharmaceutical, AstraZeneca KK, Novartis Pharma KK, AbbVie; Financial Interests, Personal, Other, Personal Fees: Chugai Pharmaceutical, AstraZeneca KK, Taiho Pharmaceutical, Boehringer Ingelheim Japan Inc., Eli Lilly KK, Ono Pharmaceutical, Merck Sharp & Dohme KK. J. Hawkins, R.E. Yanes, O. Homann, M. Tan, E. Finger: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. H. Borghaei: Financial Interests, Personal, Other, Research Support: Millennium, Merck, Celgene, BMS, Lilly; Financial Interests, Personal, Advisory Board: BMS, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantagria AB, Amgen, AbbVie, Axiom.
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