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Table 2

From: Future perspectives: targeting fibroblast growth factor receptor 1 to enhance the efficacy of immunotherapy

Table 2. Potential therapeutic strategy of FGFR1 inhibition

Strategy	Agent(s)	Target/Mechanism	Key outcomes	Limitations/Notes
Non-selective FGFR TKIs	BGJ398, AZD4547, JNJ-42756493	FGFR1–3 inhibition (intracellular TK domain)	Limited efficacy; e.g., 11% PR in FGFR1-amplified NSCLC (BGJ398)	Resistance, off-target toxicity, limited durable responses
Selective FGFR TKIs	Pemigatinib	FGFR1 rearrangement (hematologic malignancies)	78% CR in relapsed/refractory MLNs (FIGHT-203 study); FDA approved	High efficacy in specific FGFR1-fusion-driven hematologic cancers
	Alofanib	Selective extracellular FGFR inhibitor	Promising preclinical and clinical data	FGFR2-specific
	Futibatinib	Pan-FGFR inhibitor	Ongoing trials in FGFR1-positive tumors	Still under clinical investigation
Monoclonal antibodies	OM-RCA-01	Binds FGFR1 extracellular domain	Decrease proliferation in lung/RCC cells; tumor growth inhibition in vivo; decrease FGFR1 phosphorylation, high specificity	Ineffective in low-FGFR1 phosphorylation models (e.g., melanoma); still under clinical investigation
Combination with ICIs	OM-RCA-01 + nivolumab	FGFR1 inhibition + PD-1 blockade	Increase IFNγ (33%), increase IL-2 (74%); synergistic tumor suppression in FGFR1+/PD-L1+ lung cancer model	Lack of monotherapy control arm; mechanism of synergy not fully understood
CAF-targeted immunotherapy combination	OM-RCA-01 + nivolumab in CAF-positive TME	Immune evasion reversal via FGFR1 inhibition	Decrease tumor growth; restored IFNγ/IL-2 secretion; mitigated CAF-driven resistance	Further mechanistic exploration needed

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FGFR: fibroblast growth factor receptor; TKIs: tyrosine kinase inhibitors; PR: partial response; NSCLC: non-small cell lung cancer; CR: complete response; MLNs: myeloid/lymphoid neoplasms; RCC: renal cell carcinoma; ICIs: immune checkpoint inhibitors; IFNγ: interferon-gamma; PD-L1: programmed death-ligand 1; CAF: cancer-associated fibroblast; TME: tumor microenvironment

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