First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors

Open to people ages 18 years and up

• Histologically or cytologically confirmed unresectable or metastatic solid tumor
• Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor
• Additional FGFR2 alterations/tumor types may be considered for the Part 1 dose escalation
• Part 2 dose expansion patients must additionally meet the group requirements detailed below.
• Group 1: patient must have a confirmed diagnosis of unresectable or metastatic ICC with FGFR2 fusion (per local assessment of blood and/or tumor) and has received prior treatment with a pan-FGFR inhibitor (eg, pemigatinib, erdafitinib, infigratinib, futibatinib).
• Group 2: patient must have a confirmed diagnosis of unresectable or metastatic ICC with FGFR2 fusion (per local assessment of blood and/or tumor) and has NOT received prior treatment with a pan-FGFR inhibitor (eg, pemigatinib, erdafitinib, infigratinib, futibatinib).
• Group 3: patient has an unresectable or metastatic solid tumor with FGFR2 fusion (per local assessment of blood and/or tumor) other than ICC.
• Group 4: patient has an unresectable or metastatic solid tumor with FGFR2 amplification (per local assessment of blood and/or tumor).
• Group 5: patient has an unresectable or metastatic solid tumor with an oncogenic FGFR2 mutation (per local assessment of blood and/or tumor).
• 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

• Ongoing, clinically significant FGFR inhibitor-induced retinal detachment or an ongoing clinically significant corneal or retinal disorder
• Patient does not have adequate organ function (defined in protocol)
• Patient has active infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) (defined in protocol)
• QT interval corrected using Fridericia's formula (QTcF) > 480 msec or history of prolonged QT syndrome, Torsades de pointes or familial history of prolonged QT syndrome
• Clinically significant, uncontrolled cardiovascular disease
• CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms