A Phase II, 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

Study Identifier:
ELE-4008-202
CT.gov Identifier:
NCT07359820
EudraCT Identifier:
202552392322
EU Trial (CTIS) Number:
2025-523923-22-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

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.

To further evaluate the efficacy and safety of lirafugratinib 70 mg in 20-30 subjects across 20 sites with FGFR2 f/r, previously treated, unresectable, locally advanced or metastatic, non-CCA solid tumors who have not received prior FGFR inhibitor therapy.

Main objective (English)

To evaluate the efficacy of lirafugratinib by ORR assessed by IRC

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Solid Tumor
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
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.
  • as per ctis:
  • 1. Subject is willing and able to provide informed consent for the study prior to the performance of any study-specific procedures.
  • 2. Male or female subject ≥18 years of age.
  • 3. Subject has a measurable disease per RECIST v1.1.
  • 44. Subject has unresectable, locally advanced, or metastatic solid tumor (other than CCA) with FGFR2 f/r as detected by DNA or RNA sequencing or break-apart fluorescence in situ hybridization (defined in Appendix H), per local assessment of blood and/or tumor.. Subject has unresectable, locally advanced, or metastatic solid tumor (other than CCA) with FGFR2 f/r as detected by DNA or RNA sequencing or break-apart fluorescence in situ hybridization (defined in Appendix H), per local assessment of blood and/or tumor.
  • 5. Subject has been previously (>30 days) treated with ≥1 line of systemic therapy including chemotherapy (e.g., gemcitabine/cisplatin), immunotherapy, radiation therapy, or other approved therapies.
  • 6. Subject has not received prior treatment with an FGFRi.
  • 7. Subject has an ECOG performance status of 0 or 1.
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.
  • as per ctis:
  • 1. Subject has uncontrolled comorbidity.
  • 2. Subject has cancer other than FGFR2 f/r and has a known primary driver alteration that is amenable to approved targeted therapy (e.g., EGFR, ALK, ROS1, RET, HER2, BRAF, IDH1, KRAS). However, the subject may be eligible after consultation with the Sponsor.
  • 3. Subject does not have the following adequate organ function assessments within 7 days prior to the first dose of lirafugratinib: a. Platelet count ≥75×109/L (platelet transfusion may be used to reach 75×109/L but must have been administered at least 2 weeks prior to the first dose of lirafugratinib) b. Absolute neutrophil count ≥1×109/L c. 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 lirafugratinib) d. Aspartate aminotransferase or alanine aminotransferase <3× the upper limit of normal (ULN) if no hepatic metastases are present and <5×ULN if hepatic metastases are present e. Total bilirubin <1.5×ULN; <3×ULN, with direct bilirubin <1.5×ULN in the presence of Gilbert’s disease f. Estimated (including Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas [Appendix A]) or measured creatinine clearance >50 mL/min g. Serum phosphate <7.0 mg/dL (2.3 mmol/L)
  • 4. Subject has an active infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infectia. a. Active HIV infection is defined by positivity for HIV-1 or HIV-2 antibodies. Subjects who are HIV positive are allowed if all of the following criteria are met: CD4+ count ≥350/μL, undetectable viral load, receiving antiretroviral therapy (ART) that does not interact with lirafugratinib (subjects should be on established ART for at least 4 weeks), and no HIV/acquired immunodeficiency syndrome-associated opportunistic infection in the last 12 months (Uldrick 2017). b. Active HBV infection is defined by a positive HBV surface antigen (HBsAg) result. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core [HBc] antibody, absence of HBsAg, and serum HBV DNA <1000 IU/mL) are eligible (Reddy 2014, Terrault 2018). Subjects with well-controlled HBV infection, indicated by presence of HBsAg with serum HBV DNA <500 IU/mL are also eligible. c. Subjects positive for HCV antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
  • 5. Subject has a QT interval corrected using Fridericia’s formula >480 msec or a history of prolonged QT syndrome or Torsade de Pointes or a family history of prolonged QT syndrome.
  • 6. Subject has clinically significant, uncontrolled cardiovascular disease, including congestive heart failure Class III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months; uncontrolled hypertension (Grade 3 or higher); or clinically significant, uncontrolled arrhythmia, including bradyarrhythmia that may cause QT prolongation (e.g., type II second-degree heart block or third-degree heart block).
  • 7. Subject has central nervous system (CNS) metastases or primary CNS tumor that is associated with progressive neurologic symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a subject requires corticosteroids for management of CNS disease, the dose of corticosteroids must have been stable for the 2 weeks preceding C1D1. Subjects with stable or asymptomatic CNS metastases or primary CNS tumor may be eligible after consultation with the Sponsor.
  • 8. Subject has received anticancer therapy (including both systemic therapy and radiotherapy) within 14 days or 5 half-lives (whichever is shorter) and immunotherapy or other antibody therapy within 28 days prior to the first dose of lirafugratinib. Lirafugratinib may be started within these washout periods if considered by the Investigator to be safe and in the best interest of the subject, with prior Sponsor approval, provided immune-related toxicities in subjects who received previous immunotherapy have resolved to
  • 9. Subject has received locoregional hepatic therapy (e.g., transcatheter arterial chemoembolization or yttrium90) within 4 weeks prior to C1D1.
  • 10. Subject has received neutrophil growth factor support within 14 days of the first dose of lirafugratinib.
  • 11. Subject requires treatment with a prohibited medication (Section 6.8.1) that cannot be discontinued at least 5 half-lives or 2 weeks (whichever is shorter) before the initiation of lirafugratinib.
  • 12. Subject has had a major surgical procedure within 14 days of the first dose of lirafugratinib (procedures such as central venous catheter placement and tumor needle biopsy are not considered major surgical procedures). Study centers should discuss other minor surgeries with the Sponsor.
  • 13. Subject has a history of another primary malignancy that has been diagnosed or required therapy within the past year. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate or breast cancer, curatively treated localized thyroid cancer, and completely resected carcinoma in situ of any site. Adjuvant hormonal therapy for previously treated breast cancer, prostate cancer, or another hormone-dependent solid tumor is not exclusionary.
  • 14. Subject is unwilling or unable to comply with scheduled visits, drug dosing regimen, laboratory tests, or other study procedures and study restrictions.
  • 15. Female subjects, if not postmenopausal or surgically sterile, are unwilling to abstain from sexual intercourse or employ highly effective contraception during the treatment period and for at least 180 days (6 months) after the last dose of lirafugratinib. Male subjects, if not surgically sterile, are unwilling to abstain from sexual intercourse or employ highly effective contraception during the treatment period and for at least 90 days (3 months) after the last dose of lirafugratinib.
  • 16. Pregnant female subjects, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy, obtained within 7 days prior to the first dose of lirafugratinib. Females with β-hCG values that are within the range for pregnancy but are not pregnant (false positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral oophorectomy; total hysterectomy) do not require a serum β-hCG test.
  • 17. Female subjects who are breastfeeding.
  • 18. Subject has prior or ongoing clinically significant disease, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator’s opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of lirafugratinib; or impair the assessment of study results.
  • 19. Subject has documented history of and/or ongoing clinically significant ectopic mineralization/calcification.
  • 20. Subject has known systemic hypersensitivity to lirafugratinib drug substance or inactive ingredients.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Status
Will Be Recruiting
Condition(s) Treated at Site
Solid Tumor