RECRUITING

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

Conditions

Advanced Urothelial Carcinoma Oral Drug Administration Open Label

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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, as a monotherapy and in combination with Pembrolizumab * What is the right dose level for patients Participants will be asked to take FX-909 daily in tablet form, or FX-909 daily and Pembrolizumab every 3 weeks, 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.

Official Title

A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909 (as Monotherapy or in Combination With Pembrolizumab) in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma

Quick Facts

Study Start:2023-08-24

Study Completion:2028-01-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05929235

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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. An archival, paraffin-embedded, formalin-fixed, tumor sample (see Laboratory Manual for details) that in Part A is no more than 30 months old at the time of screening or in Part B is no more than 30 months old at time of pre-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. 5. Part A: 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. 6. Part A: Patients with or without measurable disease (as defined by RECIST version 1.1) will be eligible for enrollment.	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. (See Exclusion Criterion 6 for required radiotherapy windows.) 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. Patients requiring adjuvant therapy within the past 2 years for another malignancy will not be considered to have been cured. 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 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. Patients 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 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: * 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 8. 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. 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.

Inclusion Criteria

Exclusion Criteria

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. An archival, paraffin-embedded, formalin-fixed, tumor sample (see Laboratory Manual for details) that in Part A is no more than 30 months old at the time of screening or in Part B is no more than 30 months old at time of pre-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.
5. Part A: 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.
6. Part A: Patients with or without measurable disease (as defined by RECIST version 1.1) will be eligible for enrollment.

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. (See Exclusion Criterion 6 for required radiotherapy windows.)
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. Patients requiring adjuvant therapy within the past 2 years for another malignancy will not be considered to have been cured.
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 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. Patients 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 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:
* 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 8. 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.
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.

Contacts and Locations

Study Contact

Jennifer Tepper, Associate Director, Clinical Operations

CONTACT

9083097228

clinops@flaretx.com

Carolyn McCrone, Sr Clinical Trial Associate

CONTACT

clinops@flaretx.com

Principal Investigator

Gopa Iyer, MD

PRINCIPAL_INVESTIGATOR

Memorial Slone Kettering

Study Locations (Sites)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158

United States

Yale Cancer Center

New Haven, Connecticut, 06519

United States

The University of Chicago Medicine

Chicago, Illinois, 60637

United States

Mass General Cancer Center

Boston, Massachusetts, 02114

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

United States

Memorial Slone Kettering Cancer Center

New York, New York, 10065

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514

United States

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195

United States

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

United States

Houston Methodist Cockrell Center for Advanced Therapeutics

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Flare Therapeutics Inc.

Gopa Iyer, MD, PRINCIPAL_INVESTIGATOR, Memorial Slone Kettering

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-08-24

Study Completion Date2028-01-30

Study Record Updates

Study Start Date2023-08-24

Study Completion Date2028-01-30

Terms related to this study

Additional Relevant MeSH Terms

Advanced Urothelial Carcinoma
Oral Drug Administration
Open Label