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 - Patients must have unresectable or metastatic intrahepatic cholangiocarcinoma with FGFR2 fusion previously treated with a pan-FGFR inhibitor
• Group 2 - Patients must have unresectable or metastatic intrahepatic cholangiocarcinoma with FGFR2 fusion NOT previously treated with a pan-FGFR inhibitor
• Group 3 - Patients must have unresectable or metastatic solid tumor with FGFR2 fusion other than ICC
• Group 4 - Patients must have unresectable or metastatic solid tumor with FGFR2 amplification
• Group 5 - Patients must have unresectable or metastatic solid tumor with an oncogenic FGFR2 mutation
• 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 0-2

• Ongoing, clinically significant corneal or retinal disorder
• Patient has any of the following within 14 days prior to the first dose of RLY-4008:

• Platelet count < 75 x 10⁹ /L

• Absolute neutrophil count (ANC) < 1 x 10⁹ /L

• Hemoglobin < 8 g/dL (red blood cell transfusion and erythropoietin may be used to reach 8 g/dL, but must have been administered at least 2 weeks prior to the first dose of RLY-4008)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x the upper limit of normal (ULN) if no hepatic metastases are present; > 5 x ULN if hepatic metastases are present
• Total bilirubin > 1.5 x ULN; > 3 x ULN with direct bilirubin > 1.5 x ULN in presence of Gilbert's disease
• Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 50 mL/min
• 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