FX-909 for Bladder Cancer

Recruiting at 10 trial locations

Overseen By Carolyn McCrone, Sr Clinical Trial Associate

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Flare Therapeutics Inc.

Must not be taking: Insulin, Steroids, Anticancer, others

Disqualifiers: Pregnancy, HIV, Hepatitis, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether FX-909, a new potential drug, is safe and what dose works best for treating advanced solid tumors, including bladder cancer. Participants will take a daily tablet and undergo tests to help researchers understand the drug's effects. People with advanced urothelial carcinoma, a type of bladder cancer, who have tried other treatments without success, might be a good fit for this study. Participants must attend regular hospital visits for scans and sample collections. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you need certain treatments, like high doses of steroids or other prohibited therapies during the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that FX-909 is likely to be safe for humans?

Research has shown that FX-909 has been safe in studies so far. Earlier research found that participants generally tolerated the treatment well. These studies examined the treatment's safety and its mechanism in the body. No major safety issues have been reported yet, but the research is still in its early stages. As FX-909 is still undergoing early testing, participants in this trial will help determine its safety and the optimal dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for bladder cancer, such as chemotherapy and immunotherapy, work by targeting rapidly dividing cells or boosting the immune system to attack cancer. But FX-909 is different because it explores a new approach with its novel active ingredient that specifically targets cancer cells, potentially reducing harm to healthy tissues. This unique mechanism of action could offer a more precise treatment, minimizing side effects commonly associated with current therapies. Researchers are excited about FX-909 because it represents a promising shift towards more targeted cancer treatments, which could improve patient outcomes and quality of life.

What evidence suggests that FX-909 might be an effective treatment for bladder cancer?

Research has shown that FX-909, a new treatment under investigation in this trial, has potential in treating advanced bladder cancer. Early results suggest that FX-909 can work independently. This drug is unique because it alters certain proteins in cancer cells to slow their growth. Safety data indicate that only 10% of patients experienced serious blood-related side effects. Although it's still early, these findings offer hope for better outcomes for patients with this challenging type of cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Gopa Iyer, MD

Principal Investigator

Memorial Slone Kettering

Are You a Good Fit for This Trial?

This trial is for adults (18+) with advanced solid tumors, including urothelial carcinoma, that have worsened after standard treatments or when such treatments aren't suitable. Participants must be in relatively good health otherwise (ECOG status 0-2), able to consent, and have a tumor sample available. Pregnant or breastfeeding women, individuals with recent serious heart issues, uncontrolled infections like HIV/HCV, severe lung function impairment, certain gastrointestinal disorders, or those who've had recent chemotherapy are excluded.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and has not responded to or cannot be treated with standard therapies.

Patients with or without measurable disease (as defined by RECIST version 1.1) will be eligible for enrollment

I can understand and am willing to sign a consent form.

Exclusion Criteria

I have stable brain metastases with no symptoms after radiotherapy.

I haven't had major surgery in the last 4 weeks.

I have lipodystrophy or need medication that causes it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive FX-909 in a dose-escalation phase to determine the preliminary recommended phase 2 dose (RP2D)

28-day cycles

Multiple site visits for blood tests and sample collection

Monotherapy Expansion

Further evaluation of safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of FX-909 in patients with locally advanced and metastatic urothelial carcinoma

28-day cycles

Regular CT/MRI scans and site visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FX-909

Trial Overview The study tests the safety and appropriate dosage of FX-909 taken orally by patients with advanced cancers. It involves daily intake of FX-909 tablets while monitoring effects through regular site visits for blood tests and imaging scans like CT/MRI to assess how the body responds to the treatment over time.

How Is the Trial Designed?

Group I: Expansion Expansion Experimental Treatment 1 Intervention

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.

Group II: Dose Escalation Experimental Treatment 1 Intervention

3+3 design, 5 dose levels

Who Is Running the Clinical Trial?

Flare Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

80+

Published Research Related to This Trial

In a study of 45 patients with high-risk bladder cancer, the combination of transurethral resection of the bladder tumor (TURB) with concurrent cisplatin, 5-fluorouracil (5-FU), and radiation therapy resulted in an impressive 87% complete response rate, with 64% of patients remaining tumor-free after treatment.

The treatment protocol demonstrated acceptable safety, with only 10% experiencing severe hematologic toxicity and a 5-year survival rate of 54% with preserved bladder, indicating its efficacy and potential as a viable option for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ preservation in patients with invasive bladder cancer: initial results of an intensified protocol of transurethral surgery and radiation therapy plus concurrent cisplatin and 5-fluorouracil. Rödel, C., Grabenbauer, GG., Kühn, R., et al.[2019]

Bladder cancer, often linked to environmental and lifestyle factors, shows promising outcomes with early intervention; 87% of early-stage patients can achieve 10-year survival after appropriate treatment, although many still require radical cystectomy.

Recent studies suggest that the gemcitabine and cisplatin regimen is as effective as traditional chemotherapy with less toxicity, making it the new standard for advanced bladder cancer treatment in ongoing phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder cancer. Patton, SE., Hall, MC., Ozen, H.[2022]

In a study of 6007 urothelial cancer patients, those who received enfortumab vedotin after pembrolizumab had significantly longer overall survival compared to those treated with paclitaxel or docetaxel, indicating its effectiveness as a life-prolonging therapy.

Enfortumab vedotin was identified as an independent risk factor for improved overall survival, suggesting it may be a valuable treatment option for Japanese patients with advanced urothelial carcinoma following prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma. Kawahara, T., Hasizume, A., Uemura, K., et al.[2023]

A study of 248 patients who underwent radical cystectomy for bladder cancer showed a 5-year survival rate of 69%, indicating that this surgical approach can be effective for managing bladder cancer, especially for tumors confined to the bladder.

Key risk factors for bladder cancer-specific death included extravesical tumor growth, high tumor grade, and positive lymph-node status, highlighting the importance of these factors in predicting patient outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty-year experience of radical cystectomy for bladder cancer in a medium-volume centre. Boström, PJ., Mirtti, T., Kössi, J., et al.[2022]

Vinflunine, while authorized for second-line treatment of advanced urothelial carcinoma, only increased median overall survival by 2 months compared to palliative care alone, which is not statistically significant in primary analyses.

The drug has a similar adverse effect profile to other vinca alkaloids, including serious hematological disorders and cardiac issues, leading to an unfavorable risk-benefit balance for patients with bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinflunine. [2013]

A predictive nomogram developed from a study of 220 bladder cancer patients undergoing radical cystectomy showed a 27.3% incidence of urinary tract infections (UTIs) within 90 days, with common pathogens including Enterococcus and Escherichia coli.

The nomogram demonstrated high predictive accuracy with a C-index of 0.858, indicating it can effectively identify patients at risk for UTIs post-surgery, incorporating factors like urinary diversion type and comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Warning Models to Predict the 90-Day Urinary Tract Infection Risk After Radical Cystectomy and Urinary Diversion for Patients With Bladder Cancer. Lu, X., Jiang, H., Wang, D., et al.[2022]

The FAP combination chemotherapy demonstrated a high response rate in advanced urothelial cancer, with 65% of patients showing objective responses, including 18% achieving complete responses, based on a study of 34 patients.

The treatment had manageable toxicity, with significant hematologic toxicity (grade 3-4 neutropenia) occurring in 44% of patients, while non-hematologic side effects were minimal, indicating that FAP is a promising first-line option for this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Fluorouracil, interferon-alpha-2b and cisplatin (FAP) for advanced urothelial cancer. A phase II study. Hellenic Co-operative Oncology Group. Kosmidis, PA., Bacoyiannis, C., Fountzilas, G., et al.[2020]

In a study of 106 patients with advanced urothelial cancer, the addition of Factor AF2 to chemotherapy resulted in increased myelotoxicity and gastrointestinal side effects compared to chemotherapy alone, indicating a potential safety concern.

Despite the supportive effects of Factor AF2, there was no significant difference in tumor response, median survival (33 weeks), or time to progression (20 weeks) between patients receiving Factor AF2 and those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the complementary drug Factor AF2 as a supportive agent in management of advanced urothelial carcinoma. Prospective randomized multicenter study]. Krege, S., Hinke, A., Otto, T., et al.[2019]

Citations

1. flaretx.com flaretx.com/fx-909/

FX-909 The five-year survival rate for metastatic UC remains poor, with estimates below 6%. While the introduction of checkpoint inhibitors and targeted therapies has ...

2. flaretx.com flaretx.com/flare-therapeutics-presents-part-a-data-from-fx-909-phase-1-study-at-aacr-nci-eortc-international-conference/

Flare Therapeutics Presents Part A Data from FX-909 ... FX-909, the first small molecule targeting PPARG to be tested in humans, showed monotherapy activity in advanced urothelial carcinoma with a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05929235

NCT05929235 | A Study of FX-909 in Patients With ... The goal of this clinical trial is to study the safety and tolerability in all advanced solid tumors, including advanced urothelial carcinoma.

4. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.5c01252

Structural Basis of PPARγ-Mediated Transcriptional ... FX-909 is a covalent PPARγ inverse agonist in phase 1 clinical trials for advanced solid malignancies, including muscle-invasive bladder cancer.

5. withpower.com withpower.com/trial/phase-1-carcinoma-7-2023-2c0c4

FX-909 for Bladder Cancer The treatment protocol demonstrated acceptable safety, with only 10% experiencing severe hematologic toxicity and a 5-year survival rate of 54% with preserved ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.TPS709

A phase 1, first-in-human, dose-escalation and expansion ... One treatment cycle is 28 days. Dose expansion will evaluate the safety, PK/PD profile, and antitumor activity of FX-909 at the RP2D.

7. biospace.com biospace.com/press-releases/flare-therapeutics-presents-part-a-data-from-fx-909-phase-1-study-at-aacr-nci-eortc-international-conference

Flare Therapeutics Presents Part A Data from FX-909 ... FX-909 has an acceptable safety and ... bladder cancer, representing approximately 25% of all bladder cancers diagnosed each year.

8. urologytimes.com urologytimes.com/view/phase-1b-trial-of-pparg-inhibitor-launches-in-urothelial-carcinoma

Phase 1B trial of PPARG inhibitor launches in urothelial ... FX-909 is an investigational small molecule PPARG inhibitor for patients with locally advanced or metastatic urothelial carcinoma.