Overview

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

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.