...- Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor...

...Main inclusion criteria:• Patient must have disease that is refractory to standard therapy, disease that has not adequately responded to standard therapy, disease for which standard or curative therapy does not exist, or the patient must be intolerant to or have declined standard therapy.• Patient must have measurable or evaluable disease per RECIST v1.1.• Patient has ECOG performance status of 0-1.Part 1 dose escalation patients must additionally meet the group requirements detailed below:• Histologically or cytologically confirmed unresectable or metastatic solid tumor• Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor. ...

Anti-tumor activity was observed in CCA and solid tumors across doses and FGFR2 alterations with radiographic tumor reductions in 74 (64%), SD/PR in 83 (72%)...Clinically meaningful disease control and durable responses were observed in pts with FGFR2 f/r CCA....These encouraging dose escalation data confirm the broad therapeutic potential of highly selective FGFR2 targeting with RLY-4008 by demonstrating encouraging initial efficacy across FGFR2-altered solid tumors and genomic alterations, with a differentiated safety profile that avoids FGFR1- and FGFR4-related toxicity.

Potent efficacy was observed across all doses, particularly at the RP2D with an ORR of 88%...RLY-4008 is a promising next-generation inhibitor with potential to transform the treatment of FGFR2 f/r, FGFRi-naïve CCA.