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

Purpose

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 4 parts: a dose escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3) and a rollover (Part 4).

Conditions

  • FGFR2 Amplification
  • FGFR2 Gene Mutation
  • FGFR2 Gene Fusion/Rearrangement
  • FGFR2 Gene Translocation
  • FGFR2 Gene Activation
  • Intrahepatic Cholangiocarcinoma
  • Cholangiocarcinoma
  • Other Solid Tumors, Adult

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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: o CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi - Part 4: - Patient is receiving RLY-4008 on RLY-4008-101 study and benefiting from treatment as assessed by the investigator.

Exclusion Criteria

  • Parts 1, 2, and 3 - 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 - Part 4: - Patient has permanently discontinued treatment with RLY-4008 for any reason before enrolling into Part 4.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Part 1 (multiple ascending doses): • Unresectable or metastatic CCA or other unresectable or metastatic solid tumor Part 2 (RP2D determined in Part 1): - Group 1: CCA patients w/ an FGFR2 fusion previously treated w/ an FGFRi treatment - Group 2: CCA patients w/ an FGFR2 fusion w/ prior chemotherapy but no prior FGFRi treatment - Group 3: Non-CCA patients w/ an FGFR2 fusion and no prior FGFRi - Group 4: Non-CCA patients w/ an FGFR2 amplification and no prior FGFRi treatment - Group 5: Non-CCA patients w/ an FGFR2 mutation and no prior FGFRi treatment - Group 6: CCA patients w/ an FGFR2 fusion with no prior chemotherapy and no prior FGFRi treatment - Group 7: CCA patients w/ an FGFR2 mutation or amplification and no prior FGFRi treatment Part 3 (Extension of Part 2, Group 2): • CCA patients w/ an FGFR2 fusion with prior chemotherapy but no prior FGFRi treatment Part 4 (Rollover): • Ongoing Parts 1, 2, and 3 patients enrolled on study and receiving RLY-4008
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1: Dose Escalation 		Multiple doses of RLY-4008 for oral administration.
  • Drug: RLY-4008
    RLY-4008 is an oral inhibitor of FGFR2
Experimental
Part 2: Dose Expansion 		Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
  • Drug: RLY-4008
    RLY-4008 is an oral inhibitor of FGFR2
Experimental
Part 3: Extension 		Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
  • Drug: RLY-4008
    RLY-4008 is an oral inhibitor of FGFR2
Experimental
Part 4: Rollover 		Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
  • Drug: RLY-4008
    RLY-4008 is an oral inhibitor of FGFR2

More Details

Status
Active, not recruiting
Sponsor
Elevar Therapeutics

Study Contact