REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors
- Interventional
- Recruiting
- NCT04526106
Contact Information
A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors
This is a Phase 1/2, open-label, FIH study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDy), and antineoplastic activity of RLY-4008, a potent and highly selective FGFR2 inhibitor, in patients with unresectable or metastatic cholangiocarcinoma (CCA) and other solid tumors. The study consists of 3 parts: a dose escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3).
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
Key Inclusion Criteria
- Histologically or cytologically confirmed unresectable or metastatic solid tumor
- Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor
- Patient must have measurable disease per RECIST v1.1
- Patient has ECOG performance status of 0-1
- 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
- Part 2 dose expansion patients with Cholangiocarcinoma:
- Group 1: CCA patients with an FGFR2 fusion previously treated with an FGFRi
- Group 2: CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
- Group 6: CCA patients with an FGFR2 fusion with no prior chemotherapy and not previously treated with an FGFRi. Prior adjuvant/neo-adjuvant treatment completed >6 months before enrollment is acceptable. Up to 2 cycles of palliative chemotherapy are allowed during screening
- Group 7: CCA patients with an FGFR2 mutation or amplification and not previously treated with an FGFRi. Note: For Group 7, patients with confirmed diagnosis of unresectable or metastatic CCA with an FGFR2 fusion are not eligible.
- Part 2 dose expansion patients with other solid tumors (NOT Cholangiocarcinoma):
- Group 3: Non-CCA patients with an FGFR2 fusion and not previously treated with an FGFRi.
- Group 4: Non-CCA patients with an FGFR2 amplification and not previously treated with an FGFRi.
- Group 5: Non-CCA patients with an FGFR2 mutation and not previously treated with an FGFRi
- Part 3 extension:
- CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
Key Exclusion Criteria
- Ongoing, clinically significant FGFRi-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). Patients with well-controlled HBV are eligible (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
- Histologically or cytologically confirmed unresectable or metastatic solid tumor
- Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor
- Patient must have measurable disease per RECIST v1.1
- Patient has ECOG performance status of 0-1
- 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
- Part 2 dose expansion patients with Cholangiocarcinoma:
- Group 1: CCA patients with an FGFR2 fusion previously treated with an FGFRi
- Group 2: CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
- Group 6: CCA patients with an FGFR2 fusion with no prior chemotherapy and not previously treated with an FGFRi. Prior adjuvant/neo-adjuvant treatment completed >6 months before enrollment is acceptable. Up to 2 cycles of palliative chemotherapy are allowed during screening
- Group 7: CCA patients with an FGFR2 mutation or amplification and not previously treated with an FGFRi. Note: For Group 7, patients with confirmed diagnosis of unresectable or metastatic CCA with an FGFR2 fusion are not eligible.
- Part 2 dose expansion patients with other solid tumors (NOT Cholangiocarcinoma):
- Group 3: Non-CCA patients with an FGFR2 fusion and not previously treated with an FGFRi.
- Group 4: Non-CCA patients with an FGFR2 amplification and not previously treated with an FGFRi.
- Group 5: Non-CCA patients with an FGFR2 mutation and not previously treated with an FGFRi
- Part 3 extension:
- CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
Key Exclusion Criteria
- Ongoing, clinically significant FGFRi-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). Patients with well-controlled HBV are eligible (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
- Breast Cancer
- Endometrial Cancer
- Gastric Cancer
- Solid Tumors
- Cholangiocarcinoma