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

NCT05929235 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: FX-909-CLINPRO-13. KEYNOTE-G54 4. MK-3475-G54
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 12

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, 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.

Conditions

Oral Drug Administration; Advanced Urothelial Carcinoma; Open Label

Outcome Measures

Primary Outcomes (1)

• To assess dose-limiting toxicities, the incidence and severity of adverse events and serious adverse events associated with FX-909 (Safety and Tolerability)

  Incidence of dose-limiting toxicities (DLTs); Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  through study completion, an average of 3 years

Secondary Outcomes (13)

• To define the preliminary recommended phase 2 dose of FX-909, and/or maximum tolerated dose (MTD)

  through study completion, an average of 3 years

• To characterize the pharmacokinetic profile of FX-909 in patients with advanced solid malignancies

  through study completion, an average of 3 years

• To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies

  through study completion, an average of 3 years

• To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies

  through study completion, an average of 3 years

• To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies

  through study completion, an average of 3 years

Study Arms (3)

Dose Escalation

EXPERIMENTAL

3+3 design, 5 dose levels

Drug: FX-909

Expansion Expansion

EXPERIMENTAL

Part B will proceed in a 2-stage design that will investigate 2 dose arms of FX-909 in Stage 1; with a single arm in Stage 2 envisioned.

Drug: FX-909

FX-909 in Combination with Pembrolizumab

EXPERIMENTAL

Part 1A1 will be a dose-escalation study to investigate FX-909 in combination with Pembrolizumab.

Drug: FX-909; Drug: Pembrolizumab (KEYTRUDA ®); Drug: KEYTRUDA ®( Pembrolizumab)

Interventions

Pembrolizumab (KEYTRUDA ®) DRUG

Pembrolizumab is an immunotherapy checkpoint inhibitor.

FX-909 in Combination with Pembrolizumab

KEYTRUDA ®( Pembrolizumab) DRUG

Keytruda is an immunotherapy checkpoint inhibitor.

FX-909 in Combination with Pembrolizumab

FX-909 DRUG

FX-909 is an orally available new molecular entity that inhibits basal- and ligand-activated transcription by PPARG.

Dose Escalation; Expansion Expansion; FX-909 in Combination with Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and willing to sign an informed consent.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• 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.
• 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.
• Part B: Patients with histologically or cytologically confirmed, locally advanced (unresectable) or metastatic urothelial carcinoma exhibiting high levels of PPARG protein expression will be prospectively enrolled in this study. Eligibility will require a Tumor Positivity Score (TPS) of ≥ 60%, as determined by an investigational immunohistochemistry (IHC) assay for PPARG.
• Treated with ≤ 4 prior therapies for advanced or metastatic disease Patients in Part B must have progressed after all available standard therapy, been unable to tolerate standard therapy, or be considered inappropriate for standard therapy by the Investigator.
• Part A: Patients with or without measurable disease (as defined by RECIST version 1.1) will be eligible for enrollment.
• Part B: 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.
• \. Screening laboratory values meet the criteria outlined in Table 8.

You may not qualify if:

• Female patients who are pregnant (confirmed with a positive pregnancy test) or breastfeeding.
• Prior therapy directly inhibiting PPARG or RXRA.
• 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.
• Prior major surgery (excluding placement of vascular access) within 4 weeks before study drug administration.
• 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.
• 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.
• 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.
• Known active diagnosis of lipodystrophy/lipoatrophy, or an ongoing need to receive medications known to cause lipodystrophy/lipoatrophy.
• Any active uncontrolled systemic bacterial, viral, or fungal infection requiring treatment.
• Known history of HIV seropositivity. Those who have no detectable viral load on highly active antiretroviral therapy (HAART) are permitted.
• 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.
• Active hepatitis C virus (HCV) infection. Those who have completed curative therapy for HCV and have no detectable viral load are permitted.
• 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.
• Significant impairment of lung function indicated by resting oxygen saturations below 92% on room air or requiring chronic use of ambulatory supplemental oxygen.
• 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.

Sponsors & Collaborators

• Flare Therapeutics Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06519, United States

RECRUITING

Sylvester Comprehensive Cancer Center, University of Miami

Miami, Florida, 33136, United States

RECRUITING

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

RECRUITING

Mass General Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Memorial Slone Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514, United States

RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Houston Methodist Cockrell Center for Advanced Therapeutics

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Galsky MD, Mantia C, Bowden M, Bellmunt J, Garmezy B, Iyer G, Petrylak DP, Rasco D, Gupta S, Rodriguez-Rivera I, Mikhailov Y, Joshi A, Nguyen PA, Kakrecha B, Tepper J, Costa AM, McCrone C, Rossi AP, Mertz JA, Gjini E, Meyers ML, Milowsky MI, Gao X. A small-molecule inverse agonist of PPARgamma for advanced solid tumors: a phase 1 trial. Nat Med. 2026 Feb 28. doi: 10.1038/s41591-026-04263-3. Online ahead of print.

  PMID: 41760953 DERIVED

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Gopa Iyer, MD

  Memorial Slone Kettering

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Janine Koucheki, Associate Director, Clinical Operations

CONTACT

857-706-4400; clinops@flaretx.com

Carolyn McCrone, Sr Clinical Trial Associate

CONTACT

clinops@flaretx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A is a 3+3 dose escalation design. Part B will proceed in a 2-stage design that will investigate 2 dose arms of FX-909 in Stage 1; with a single arm in Stage 2 envisioned. Part 1A1 is a dose escalation to investigate FX-909 in combination with Pembrolizumab.

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: July 3, 2023
• Study Start: August 24, 2023
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): January 30, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR

Locations

US (12)