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A Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05929235
Recruitment Status : Recruiting
First Posted : July 3, 2023
Last Update Posted : March 21, 2024
Sponsor:
Information provided by (Responsible Party):
Flare Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE May 30, 2023
First Posted Date  ICMJE July 3, 2023
Last Update Posted Date March 21, 2024
Actual Study Start Date  ICMJE September 13, 2023
Estimated Primary Completion Date September 30, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2023)
To assess dose-limiting toxicities, the incidence and severity of adverse events and serious adverse events associated with FX-909 (Safety and Tolerability) [ Time Frame: through study completion, an average of 3 years ]
Incidence of dose-limiting toxicities (DLTs); Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2023)
  • To define the preliminary recommended phase 2 dose of FX-909, and/or maximum tolerated dose (MTD) [ Time Frame: through study completion, an average of 3 years ]
    Assess patients' safety measures (AEs/SAEs) in comparison with patients' objective response rates
  • To characterize the pharmacokinetic profile of FX-909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Plasma pharmacokinetic parameters of FX-909 via AUC
  • To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Plasma pharmacokinetic parameters of FX-909, via Cmax
  • To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Plasma pharmacokinetic parameters of FX-909, via Tmax
  • To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Plasma pharmacokinetic parameters of FX-909 via T½
  • To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Plasma pharmacokinetic parameters of FX-909 via renal clearance in urine
  • To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Plasma pharmacokinetic parameters of FX-909 via percentage of FX-909 in urine
  • To evaluate preliminary antitumor activity of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Objective response rate (ORR)
  • To evaluate preliminary antitumor activity of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Duration of Response (DoR)
  • To evaluate preliminary antitumor activity of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Time to response
  • To evaluate preliminary antitumor activity of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Disease Control Rate (DCR)
  • To evaluate preliminary antitumor activity of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Progression-Free Survival (PFS) based on Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
  • To evaluate preliminary antitumor activity of FX 909 in patients with advanced solid malignancies [ Time Frame: through study completion, an average of 3 years ]
    Overall survival (OS)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma
Official Title  ICMJE A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma
Brief Summary

The goal of this clinical trial is to study the safety and tolerability in all advanced solid tumors, including advanced urothelial carcinoma.

The main question[s] it aims to answer are:

  • Is FX-909 safe and tolerable
  • What is the right dose level for patients

Participants will be asked to take FX-909 daily , in tablet form and record any outcomes from taking the drug. Participants will also be asked to return for multiple site visits for various blood tests and to collect blood and tumor samples as well as have regular CT/MRI scans

Detailed Description This is an open-label Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of FX-909 given orally (PO) in patients with advanced solid malignancies. Initially, FX-909 will be given in a dose-escalation phase (Part A) to determine the preliminary recommended phase 2 dose (RP2D). Part B will be a monotherapy expansion phase to further evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of FX-909 in patients with locally advanced (unresectable) and metastatic urothelial carcinoma. Throughout the study patients will be treated in 28-day cycles.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
3+3 dose escalation design with 1 expansion arm at RP2D
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors Cancer
  • Advanced Urothelial Carcinoma
  • Oral Drug Administration
  • Open Label
Intervention  ICMJE Drug: FX-909
FX-909 is an orally available new molecular entity that inhibits basal- and ligand-activated transcription by PPARG.
Study Arms  ICMJE
  • Experimental: Dose Escalation
    3+3 design, 5 dose levels,
    Intervention: Drug: FX-909
  • Experimental: Expansion Expansion
    When a preliminary RP2D has been identified (this dose may be equal to or below the MTD) evaluate the antitumor activity in locally advanced (unresectable) and metastatic urothelial carcinoma.
    Intervention: Drug: FX-909
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 26, 2023)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 30, 2027
Estimated Primary Completion Date September 30, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  1. Able to understand and willing to sign an informed consent.
  2. Age ≥ 18 years
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  4. Part A (Dose Escalation): Histologically or cytologically diagnosed, locally advanced (unresectable) or metastatic solid malignancies that have progressed after all available standard therapy for the specific tumor type, or for which no standard therapy exists. Patients for whom standard therapies are intolerable or considered inappropriate by the Investigator are eligible.

    Part B (Expansion): Histologically or cytologically diagnosed, locally advanced (unresectable) or metastatic urothelial carcinoma with defined genetic alterations. Patients in Part B must have progressed after all available standard therapy (eg, anti- programmed cell death (ligand) 1 [PD(L)1], antibody-drug conjugate[s], and platinum-based doublet chemotherapy), been unable to tolerate standard therapy, or be considered inappropriate for standard therapy by the Investigator.

  5. Part A (Dose Escalation): Patients with or without measurable disease (as defined by RECIST version 1.1) will be eligible for enrollment.

    Part B (Expansion): Patients must have measurable disease per RECIST version 1.1 with ≥ 1 site of measurable disease that has not been previously irradiated or has progressed after radiation therapy.

  6. An archival, paraffin-embedded, formalin-fixed, tumor sample (see Laboratory Manual for details) that is no more than 30 months old at the time of screening. If an archival tumor sample is not available or is older than 30 months, then the patient must consent to provide a fresh biopsy during screening.
  7. Screening laboratory values meet the criteria outlined in the protocol. Hematologic criteria may be met with transfusion of blood products or administration of G-CSF, provided they are not given within 7 days of C1D1.

Exclusion Criteria:

  1. Female patients who are pregnant (confirmed with a positive pregnancy test) or breastfeeding.
  2. Prior anticancer chemotherapy or small molecule targeted therapy, either investigational or commercially approved and available, within 2 weeks or 5 half-lives (whichever is shorter) prior to the start of study drug administration. When the most recent therapy was a biological therapy (including antibody-drug conjugates), an immune-checkpoint inhibitor (eg, anti-PD(L)1 or anti-CTLA4), or immune agonist, patients should wait 4 weeks before starting therapy with FX-909.
  3. Prior therapy directly inhibiting PPARG or RXRA.
  4. Adverse events from prior therapy that have not returned to baseline or stabilized at Grade 1 (except alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade ≤ 2 neuropathy) prior to study drug administration.
  5. Prior major surgery (excluding placement of vascular access) within 4 weeks before study drug administration.
  6. Prior radiation therapy with an inadequate washout between the last dose and the start of study drug, defined as follows: 1) at least 2 weeks for palliative radiation to the extremities for osseous bone metastases is required; and 2) at least 4 weeks for radiation to non-extremity sites is required.
  7. History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease free. Exceptions include appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, melanoma in situ status-post full-thickness resection without recurrence, Stage 1 uterine cancer, localized prostate cancer that has been treated surgically with curative intent and presumed cured, or other malignancies with an expected curative outcome.
  8. QT Interval Corrected Using Fridericia's Formula (QTcF) > 470 msec in screening, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives.
  9. Known active diagnosis of lipodystrophy/lipoatrophy, or an ongoing need to receive medications known to cause lipodystrophy/lipoatrophy
  10. Any active uncontrolled systemic bacterial, viral, or fungal infection requiring treatment.
  11. Known history of human immunodeficiency virus (HIV) seropositivity. Those who have no detectable viral load on highly active antiretroviral therapy (HAART) are permitted.
  12. Patients with chronic hepatitis B virus (HBV) infection (indicated by a positive HBV surface antigen and/or hepatitis B core antibody). Patietns are permitted with either universal prophylaxis or a pre-emptive treatment approach consistent with regional or national guidelines for patients who receive anticancer therapies.
  13. Active hepatitis C virus (HCV) infection. Those who have completed curative therapy for HCV and have no detectable viral load are permitted.
  14. Prior diagnosis of chronic or recurrent (> 1 episode) pancreatitis at any time or a diagnosis of acute pancreatitis within the 6 months prior to screening
  15. Significant impairment of lung function indicated by resting oxygen saturations below 92% on room air or requiring chronic use of ambulatory supplemental oxygen.
  16. Uncontrolled or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or carcinomatous meningitis. Asymptomatic brain metastasis is allowed if they have been stable after appropriate radiotherapy for 1 month.
  17. Need for treatment with high doses of oral or intravenous steroids (> 10 mg/day prednisone or equivalent). Physiologic doses of corticosteroids for treatment of endocrinopathies may be continued if the patient is on a stable dose for at least 1 month.
  18. Need or anticipated need for treatment with a prohibited therapy described in the protocol during the treatment phase of this study
  19. Concurrent participation in any other investigational therapeutic study
  20. History of any of the following cardiovascular diseases:

    • Recent history (within the 6 months prior to screening) of serious uncontrolled cardiac arrhythmia (including atrial fibrillation without adequate rate control) or clinically significant ECG abnormalities including second-degree (Type II) or third-degree atrioventricular node block
    • Documented cerebrovascular event (stroke or transient ischemic attack), cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the 6 months prior to enrollment
    • Congestive heart failure (Class III or IV) as defined by the New York Heart Association functional classification system
    • Recent history (within the past 6 months) of symptomatic pericarditis
  21. Thromboembolic events and/or bleeding disorders ≤ 28 days (eg, deep vein thrombosis or pulmonary embolism) prior to the first dose of study drug
  22. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which, in the Investigator's opinion, makes it undesirable for the patient to participate in the study or would jeopardize compliance with the protocol.
  23. Patients with type 1 diabetes mellitus, or type 2 diabetes mellitus that is not adequately controlled with diet, exercise, or oral hypoglycemic agents and/or injectable agents other than insulin (as defined by HbA1c and fasting plasma glucose criteria in Table 6. Patients taking insulin are excluded from the study. Medication for type 2 diabetes mellitus should have remained stable for the past 14 days prior to screening).
  24. Known hypersensitivity to FX-909 or any of its excipients (see Table 7 for the list of excipients)
  25. Patients with gastrointestinal disorders that may interfere with the ability to swallow tablets or absorb study medication
  26. Patient is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is a member of the study site or Sponsor staff directly involved with this study, unless prospective Institutional Review Board (IRB) or Ethics Committee (EC) approval (by chair or designee) is given allowing exception to this criterion for a specific patient.
  27. Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before study entry.
  28. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patient's safety or study results.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Melissa Moles, VP Clinical Operations 6173722515 clinops@flaretx.com
Contact: Jennifer Tepper, Senior Clinical Trial Associate 9083097228 clinops@flaretx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05929235
Other Study ID Numbers  ICMJE FX-909-CLINPRO-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: study data
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Current Responsible Party Flare Therapeutics Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Flare Therapeutics Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gopa Iyer, MD Memorial Slone Kettering
PRS Account Flare Therapeutics Inc.
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP