- |||||||||| Review, Journal: FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. (Pubmed Central) - Mar 25, 2024
The next generation of small-molecule inhibitors, such as lirafugratinib and LOXO-435, and the FGFR2-specific antibody bemarituzumab are expected to have a reduced risk of hyperphosphataemia and the ability to overcome certain resistance mutations. In this Review, we describe the development and current clinical role of FGFR inhibitors and provide perspective on future research directions including expansion of the therapeutic indications for use of FGFR inhibitors, combination of these agents with immune-checkpoint inhibitors and the application of novel technologies, such as artificial intelligence.
- |||||||||| lirafugratinib (RLY-4008) / Relay Therap
Enrollment closed, Metastases: REFOCUS: a First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients with ICC and Other Advanced Solid Tumors (clinicaltrials.gov) - Mar 5, 2024 P1/2, N=540, Active, not recruiting, Taken together, these data support the clinical development of ISM8001 as a novel, selective FGFR2/FGFR3 dual inhibitor for the potential tissue-agnostic therapy of advanced solid tumors with FGFR2/3 aberrations. Recruiting --> Active, not recruiting
- |||||||||| lirafugratinib (RLY-4008) / Relay Therap
Journal: Discovery of lirafugratinib (RLY-4008), a highly selective irreversible small-molecule inhibitor of FGFR2. (Pubmed Central) - Feb 5, 2024 Using this insight, we were able to design orthosteric binders that selectively and covalently engage the P-loop of FGFR2. Our drug discovery efforts culminated in the development of lirafugratinib (RLY-4008), a covalent inhibitor of FGFR2 that shows substantial selectivity over FGFR1 (~250-fold) and FGFR4 (~5,000-fold) in vitro, causes tumor regression in multiple FGFR2-altered human xenograft models, and was recently demonstrated to be efficacious in the clinic at doses that do not induce clinically significant hyperphosphatemia or diarrhea.
- |||||||||| Lytgobi (futibatinib) / Otsuka
Journal: Futibatinib: new targeted therapy in intrahepatic cholangiocarcinoma. (Pubmed Central) - Dec 20, 2023 Our drug discovery efforts culminated in the development of lirafugratinib (RLY-4008), a covalent inhibitor of FGFR2 that shows substantial selectivity over FGFR1 (~250-fold) and FGFR4 (~5,000-fold) in vitro, causes tumor regression in multiple FGFR2-altered human xenograft models, and was recently demonstrated to be efficacious in the clinic at doses that do not induce clinically significant hyperphosphatemia or diarrhea. No abstract available
- |||||||||| lirafugratinib (RLY-4008) / Relay Therap
Journal: RLY-4008, the first highly selective FGFR2 inhibitor with activity across FGFR2 alterations and resistance mutations. (Pubmed Central) - Jun 4, 2023 In vivo, RLY-4008 induces regression in multiple xenograft models - including models with FGFR2 resistance mutations that drive clinical progression on current pan-FGFRi - while sparing FGFR1 and FGFR4. In early clinical testing, RLY-4008 induced responses without clinically significant off-isoform FGFR toxicities, confirming the broad therapeutic potential of selective FGFR2 targeting.
- |||||||||| Review, Journal: Cholangiocarcinomes avancés et gènes de fusion. (Pubmed Central) - Dec 20, 2022
In the case of NTRK fusion, larotrectinib and entrectinib have also demonstrated their efficacy. The objectives of this review are to clarify the specific diagnostic modalities for gene fusions and to summarize the results of the main trials and developments underway for the management of advanced CCA with gene fusions.
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