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

Elevar Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

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

Treatments: Drug: RLY-4008

Study type: Interventional

Funder types: Industry

Identifiers

NCT04526106

RLY-4008-101

Details and patient eligibility

About

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).

Enrollment: 490 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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:

  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.

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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490 participants in 4 patient groups

Part 1: Dose Escalation

Experimental group

Description:

Multiple doses of RLY-4008 for oral administration.

Treatment:

Drug: RLY-4008

Part 2: Dose Expansion

Experimental group

Description:

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Treatment:

Drug: RLY-4008

Part 3: Extension

Experimental group

Description:

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Treatment:

Drug: RLY-4008

Part 4: Rollover

Experimental group

Description:

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Treatment:

Drug: RLY-4008