A Study of Lirafugratinib in Non-CCA Solid Tumors With FGFR2 Fusion or Rearrangement

Official title

A Phase 2, Open-Label, Single-Arm Study of Lirafugratinib in Patients With Previously Treated, Unresectable, Locally Advanced or Metastatic Solid Tumors (Excluding Cholangiocarcinoma) With FGFR2 Fusion or Rearrangement

Overview

The goal of this clinical trial is to evaluate if lirafugratinib is efficacious and safe to treat adult patients with previously treated, unresectable, locally advanced or metastatic solid tumors (excluding cholangiocarcinoma) harboring FGFR2 fusion or rearrangement. Participants will: * Take lirafugratinib regularly as instructed by their study doctor. * Visit the clinic as instructed for checkups and tests. * Keep a diary recording each time a dose of lirafugratinib is taken.

Interventions

• Drug Lirafugratinib
  Lirafugratinib is an oral inhibitor of FGFR2

Primary outcome measures

• Objective Response Rate (ORR) assessed by Independent Review Committee per RECIST v1.1. [Time frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months.]

Secondary outcome measures (12)

• Duration of response (DOR) assessed by Independent Review Committee per RECIST v1.1. [Time frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months.]
• Number of patients with adverse events and serious adverse events. [Time frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months.]
• Number of patients with dose interruptions. [Time frame: Every 28-day cycle until end of treatment, approximately 24 months.]
• Number of patients with dose reductions. [Time frame: Every 28-day cycle until end of treatment, approximately 24 months.]
• Number of patients with dose discontinuations. [Time frame: Every 28-day cycle until end of treatment, approximately 24 months.]
• Objective Response Rate (ORR) as assessed by Investigator per RECIST v1.1. [Time frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months.]
• Duration of Response (DOR) as assessed by Investigator per RECIST v1.1. [Time frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months]
• Disease control rate (DCR) as assessed by Investigator and Independent Review Committee per RECIST v1.1. [Time frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months.]
• Progression-free survival (PFS) as assessed by Investigator and Independent Review Committee per RECIST v1.1. [Time frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months]
• Overall survival (OS). [Time frame: Up to approximately 36 months.]
• Time to response (TTR) assessed by Investigator and Independent Review Committee per RECIST v1.1. [Time frame: Up to approximately 36 months.]
• Time to progression (TTP) assessed by Investigator and Independent Review Committee per RECIST v1.1. [Time frame: Up to approximately 36 months]

Eligibility criteria

Inclusion criteria

• Unresectable, locally advanced, or metastatic solid tumor (other than CCA).
• Documented FGFR2 gene fusion or rearrangement 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.
• Previously (>30 days) treated with ≥1 line of systemic therapy including chemotherapy (e.g., gemcitabine/cisplatin), immunotherapy, radiation therapy, or other approved therapies.
• Subject has not received prior treatment with an FGFRi.

Exclusion criteria

• An uncontrolled comorbidity.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Mayo Clinic — Phoenix
• Mayo Clinic — Jacksonville
• Moffitt Cancer Center — Tampa
• University of Chicago Medical Center — Chicago
• Massachusetts General Hospital — Boston
• Mayo Clinic — Rochester
• The University of Texas M.D. Anderson Cancer Center — Houston

France · 4 centers

• Institut Bergonie — Bordeaux
• Centre Georges François Leclerc — Dijon
• Centre Leon Berard — Lyon
• Gustave Roussy Cancer Campus — Paris

Spain · 3 centers

• START Barcelona-Hospital HM Nou Delfos — Barcelona
• Hospital Universitario Fundación Jiménez Díaz- START MADRID — Madrid
• Hospital Universitario HM Sanchinarro-START MADRID-CIOCC — Madrid

United Kingdom · 3 centers

• University College Hospital (NIHR UCLH Clinical Research Facility) — London
• Sarah Cannon Research Institute UK — London
• The Christie NHS Foundation — Manchester

South Korea · 2 centers

• Seoul National University Hospital — Seoul
• Samsung Medical Center — Seoul

Identifiers

NCT: NCT07359820 · ELE-4008-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗