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
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Advanced Solid Tumors Cancer Advanced Urothelial Carcinoma Oral Drug Administration Open Label | Drug: FX-909 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 75 participants |
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 |
Official Title: | A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma |
Actual Study Start Date : | September 13, 2023 |
Estimated Primary Completion Date : | September 30, 2026 |
Estimated Study Completion Date : | January 30, 2027 |
Arm | Intervention/treatment |
---|---|
Experimental: Dose Escalation
3+3 design, 5 dose levels,
|
Drug: FX-909
FX-909 is an orally available new molecular entity that inhibits basal- and ligand-activated transcription by PPARG. |
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.
|
Drug: FX-909
FX-909 is an orally available new molecular entity that inhibits basal- and ligand-activated transcription by PPARG. |
- 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)
- 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)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
- Able to understand and willing to sign an informed consent.
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
-
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.
-
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.
- 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.
- 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:
- Female patients who are pregnant (confirmed with a positive pregnancy test) or breastfeeding.
- 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.
- 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.
- 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 human immunodeficiency virus (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 (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.
- 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.
- 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.
- Need or anticipated need for treatment with a prohibited therapy described in the protocol during the treatment phase of this study
- Concurrent participation in any other investigational therapeutic study
-
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
- Thromboembolic events and/or bleeding disorders ≤ 28 days (eg, deep vein thrombosis or pulmonary embolism) prior to the first dose of study drug
- 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.
- 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).
- Known hypersensitivity to FX-909 or any of its excipients (see Table 7 for the list of excipients)
- Patients with gastrointestinal disorders that may interfere with the ability to swallow tablets or absorb study medication
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05929235
Contact: Melissa Moles, VP Clinical Operations | 6173722515 | clinops@flaretx.com | |
Contact: Jennifer Tepper, Senior Clinical Trial Associate | 9083097228 | clinops@flaretx.com |
United States, Arizona | |
HonorHealth | Recruiting |
Scottsdale, Arizona, United States, 85258 | |
Contact: HonorHealth Nurse Navigation Team 480-323-1791 | |
Contact 833-354-6667 | |
Principal Investigator: Sunil Sharma, MD | |
United States, Connecticut | |
Yale Cancer Center | Recruiting |
New Haven, Connecticut, United States, 06519 | |
Contact: Amanda Davis, LPN 475-321-7899 Amanda.Davis@yale.edu | |
Principal Investigator: Daniel Petrylak, MD | |
United States, Massachusetts | |
Mass General Cancer Center | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Xin Gao, MD 617-724-4000 xgao4@mgb.org | |
Principal Investigator: Xin Gao, MD | |
Dana Farber Cancer Institute | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Contact: Brian Rasp 857-215-2265 Brian_Rasp@DFCI.Harvard.edu | |
Principal Investigator: Charlene Mantia, MD, Ph.D. | |
United States, New York | |
Icahn School of Medicine at Mount Sinai | Recruiting |
New York, New York, United States, 10029 | |
Contact: Lindsay Diamond 347-514-1561 lindsay.diamond@mssm.edu | |
Contact: Erin Heath 646-901-3172 erin.heath@mssm.edu | |
Principal Investigator: Matthew Galsky, MD | |
Memorial Slone Kettering Cancer Center | Recruiting |
New York, New York, United States, 10065 | |
Contact: Gopakumar V Iyer, MD 646-888-4737 iyerg@mskcc.org | |
Principal Investigator: Gopa Iyer, MD | |
United States, North Carolina | |
UNC Lineberger Comprehensive Cancer Center | Recruiting |
Chapel Hill, North Carolina, United States, 27514 | |
Contact 877-668-0683 cancerclinicaltrials@med.unc.edu | |
Principal Investigator: Matthew Milowsky, MD | |
United States, Ohio | |
The Cleveland Clinic Foundation | Recruiting |
Cleveland, Ohio, United States, 44195 | |
Contact: Cancer Answer 216-444-7923 canceranswer@ccf.org | |
Principal Investigator: Shilpa Gupta, MD | |
United States, Tennessee | |
Sarah Cannon Research Institute | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Contact: askSARAH 844-482-4812 | |
Principal Investigator: Benjamin Garmezy, MD | |
United States, Texas | |
New Experimental Therapeutics of San Antonio (NEXT) | Recruiting |
San Antonio, Texas, United States, 78229 | |
Contact: Brianna Flores, BSN, RN 210-580-9521 bflores@nextoncology.com | |
Principal Investigator: Ildefonso Ismael Rodriguez Rivera, MD | |
South Texas Accelerated Research Therapeutics (START) | Recruiting |
San Antonio, Texas, United States, 78229 | |
Contact: Angela Galindo angela.galindo@thestartcenter.com | |
Contact: Jessie Fernandez jessie.fernandez@startsa.com | |
Principal Investigator: Drew Rasco, MD |
Principal Investigator: | Gopa Iyer, MD | Memorial Slone Kettering |
Responsible Party: | Flare Therapeutics Inc. |
ClinicalTrials.gov Identifier: | NCT05929235 |
Other Study ID Numbers: |
FX-909-CLINPRO-1 |
First Posted: | July 3, 2023 Key Record Dates |
Last Update Posted: | March 21, 2024 |
Last Verified: | March 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | study data |
Supporting Materials: |
Study Protocol Informed Consent Form (ICF) Clinical Study Report (CSR) |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Carcinoma Carcinoma, Transitional Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |