FGFR2
FGFR2 is a growth receptor fused in bile-duct cancer and overproduced in gastric cancer. This dossier gathers the 7 products (4 approved), 13 trials, 1 pathway and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
Receptor tyrosine kinase; FGFR3 alterations are the urothelial counterpart (erdafitinib).
- Cholangiocarcinoma
- Gastric
- Endometrial
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Bladder & urothelial cancer | 15-20% | FGFR3 alterations (related target) | FGFR3 mutations/fusions; erdafitinib | cBioPortal (TCGA) |
| Biliary tract cancer | 10-15% | Fusion (intrahepatic) | cBioPortal (TCGA) | |
| Gastric & gastro-oesophageal junction cancer | 3-8% | FGFR2b overexpression/amplification | FORTITUDE-101 selected IHC 2+/3+ | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mutation hotspots and which drugs address them
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| Fusions (FGFR2::BICC1 and many partners) 768 to 821 | Activating | About 10 to 15% of intrahepatic cholangiocarcinoma | Breakpoints in the last exon keep the kinase intact and add a dimerising partner. Pemigatinib and futibatinib are approved. | — | Goyal et al., Cancer Discov 2017 | |
| N550K / N550H 550 | Activating | not sourced | Molecular-brake mutation: primary driver in endometrial cancer and an acquired resistance allele after reversible FGFR inhibitors. | — | Goyal et al., Cancer Discov 2017 | |
| V565I / V565F (gatekeeper) and E566A, L618V 565 | Resistance | not sourced | Polyclonal secondary kinase-domain mutations after pemigatinib or infigratinib; the covalent inhibitor futibatinib and newer FGFR2-selective agents retain activity against several of them. | Goyal et al., Cancer Discov 2017 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: Cancer Hotspots (MSK) · COSMIC: FGFR2.
Products by modality and phase
Browse products →| Modality | Approved | Phase 3 | Withdrawn or failed |
|---|---|---|---|
| Small molecule 6 | |||
| Antibody 1 | — | — |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
| LITESPARK-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
| FORTITUDE-101 NCT05052801 | 3 | Mixed | First-line FGFR2b-overexpressing (≥10% 2+/3+), HER2-negative advanced gastric/GEJ cancer: bemarituzumab + mFOLFOX6 vs placebo + mFOLFOX6 | Interim OS 17.9 vs 12.5 months (HR 0.61); benefit attenuated on follow-up. | |
| LEAP-012 NCT04246177 | 3 | Mixed | Unresectable non-metastatic HCC: TACE + lenvatinib + pembrolizumab vs TACE + placebo | PFS HR 0.66; final OS HR 0.98. | |
| THOR NCT03390504 | 3 | Positive | Advanced urothelial cancer with FGFR3/2 alterations after chemotherapy and a checkpoint inhibitor: erdafitinib vs chemotherapy (cohort 1) | OS 12.1 vs 7.8 months, HR 0.64 (cohort 1). | |
| LEAP-002 NCT03713593 | 3 | Negative | First-line unresectable HCC: lenvatinib + pembrolizumab vs lenvatinib | OS HR 0.84, not significant. | |
| CLEAR (KEYNOTE-581) NCT02811861 | 3 | Positive | Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm) | PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79. | |
| KEYNOTE-775 / Study 309 NCT03517449 | 3 | Positive | Advanced endometrial cancer after platinum: lenvatinib + pembrolizumab vs doxorubicin or weekly paclitaxel | OS 18.3 vs 11.4 months (HR 0.62). | |
| LUME-Meso NCT01907100 | 3 | Negative | Epithelioid pleural mesothelioma, first line: cisplatin-pemetrexed ± nintedanib | PFS HR 1.01, negative. | |
| REFLECT NCT01761266 | 3 | Positive | First-line unresectable HCC: lenvatinib vs sorafenib (non-inferiority) | OS 13.6 vs 12.3 months, non-inferior (HR 0.92). | |
| FIRST-308 | 3 | Recruiting | FGFR-altered cholangiocarcinoma refractory to chemotherapy and a first-generation FGFR inhibitor: tinengotinib vs FOLFOX/FOLFIRI | ||
| FOENIX-CCA2 NCT02052778 | 2 | Positive | Previously treated FGFR2-rearranged intrahepatic cholangiocarcinoma: futibatinib single arm | ORR 42%; PFS 9.0 months; OS 21.7 months. | |
| FIGHT-202 NCT02924376 | 2 | Positive | Previously treated cholangiocarcinoma with FGFR2 fusions (cohort A): pemigatinib single arm | ORR 37%; PFS 7.0 months; OS 17.5 months. |
Resistance routes that involve this target
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways where it is a node
Pathway-to-drug matrix →- FGF / FGFR signallingNode: FGFR1-4 (FGFR2 fusions, FGFR3 mutations) · 3 druggable nodes
Fibroblast growth factor receptors are growth antennas on the cell surface. Bladder cancer mutates FGFR3, bile duct cancer fuses FGFR2 to other genes, and stomach cancer overproduces FGFR2b; each has its own drug, and each brings a tell-tale side effect (high phosphate) because the same receptors control phosphate in the kidney.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| FoundationOne CDx Foundation Medicine (Roche) · FDA CDx 2017 | NGS tissue | Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase | |
| FoundationOne Liquid CDx Foundation Medicine (Roche) · FDA CDx 2020 | NGS plasma | Per companion claim: EGFR (osimertinib, erlotinib, gefitinib), ALK (alectinib), BRCA1/2 and ATM (olaparib, rucaparib), PIK3CA (alpelisib), FGFR3 (erdafitinib), NTRK and RET; negative plasma results reflex to tissue | |
| therascreen FGFR RGQ RT-PCR Kit QIAGEN · FDA CDx 2019 | PCR | Alteration detected (erdafitinib, urothelial carcinoma) |
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →- 01
Can FGFR2-selective inhibitors overcome the polyclonal kinase-domain mutations that end responses to pemigatinib and futibatinib?
translationalindustryWhy unresolved. Resistance in cholangiocarcinoma is polyclonal (N550, V565, E566, L618) and varies between lesions; covalent and next-generation FGFR2-selective agents cover subsets, and hyperphosphataemia from FGFR1 limits dosing of pan-FGFR drugs.
What would answer it. Trials of FGFR2-selective inhibitors after FGFR-inhibitor progression with ctDNA-defined resistance profiles.
Source: Goyal et al., Cancer Discov 2017
Ideas and companies
Key papers and the live literature
Preprints →Query for this target: (TITLE:"FGFR2" OR ABSTRACT:"FGFR2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FGFR2, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/fgfr2.json. Licence CC BY 4.0.