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Brief Title: FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma

A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma

INTRODUCTION

  • Org Study ID: FX-909-CLINPRO-1
  • Secondary ID: N/A
  • NCT ID: NCT05929235
  • Sponsor: Flare Therapeutics Inc.

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.

  • Overall Status
    Recruiting
  • Start Date
    August 24, 2023
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

  • Advanced Solid Tumors Cancer
  • Advanced Urothelial Carcinoma
  • Oral Drug Administration
  • Open Label

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Gopa Iyer, MD

Role: Principal Investigator

Affiliation: Memorial Slone Kettering

Overall Contact

Name: Melissa Moles, VP Clinical Operations, Jennifer Tepper, Senior Clinical Trial Associate

Phone: 6173722515, 9083097228

Email: [email protected], [email protected]

LOCATION

Facility Status Contact
Facility: HonorHealth
Scottsdale, Arizona 85258
United States
Status: Recruiting Contact: Contact
HonorHealth Nurse Navigation Team
480-323-1791

Contact

833-354-6667

Principal Investigator
Sunil Sharma, MD

Facility: Yale Cancer Center
New Haven, Connecticut 06519
United States
Status: Recruiting Contact: Contact
Amanda Davis, LPN
475-321-7899
[email protected]

Principal Investigator
Daniel Petrylak, MD

Facility: Mass General Cancer Center
Boston, Massachusetts 02114
United States
Status: Recruiting Contact: Contact
Xin Gao, MD
617-724-4000
[email protected]

Principal Investigator
Xin Gao, MD

Facility: Dana Farber Cancer Institute
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: Contact
Brian Rasp
857-215-2265
[email protected]

Principal Investigator
Charlene Mantia, MD, Ph.D.

Facility: Icahn School of Medicine at Mount Sinai
New York, New York 10029
United States
Status: Recruiting Contact: Contact
Lindsay Diamond
347-514-1561
[email protected]

Contact
Erin Heath
646-901-3172
[email protected]

Principal Investigator
Matthew Galsky, MD

Facility: Memorial Slone Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: Contact
Gopakumar V Iyer, MD
646-888-4737
[email protected]

Principal Investigator
Gopa Iyer, MD

Facility: UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27514
United States
Status: Recruiting Contact: Contact

877-668-0683
[email protected]

Principal Investigator
Matthew Milowsky, MD

Facility: The Cleveland Clinic Foundation
Cleveland, Ohio 44195
United States
Status: Recruiting Contact: Contact
Cancer Answer
216-444-7923
[email protected]

Principal Investigator
Shilpa Gupta, MD

Facility: Sarah Cannon Research Institute
Nashville, Tennessee 37203
United States
Status: Recruiting Contact: Contact
askSARAH
844-482-4812

Principal Investigator
Benjamin Garmezy, MD

Facility: New Experimental Therapeutics of San Antonio (NEXT)
San Antonio, Texas 78229
United States
Status: Recruiting Contact: Contact
Brianna Flores, BSN, RN
210-580-9521
[email protected]

Principal Investigator
Ildefonso Ismael Rodriguez Rivera, MD

Facility: South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas 78229
United States
Status: Recruiting Contact: Contact
Angela Galindo
[email protected]

Contact
Jessie Fernandez
[email protected]

Principal Investigator
Drew Rasco, MD