Oral Erdafitinib for Bladder Cancer

Recruiting at 7 trial locations

Overseen By Gopakumar Iyer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Calcium, Phosphate, Vitamin D, others

Disqualifiers: Pregnancy, Metastatic cancer, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the effectiveness of erdafitinib in people with non-muscle invasive bladder cancer (NMIBC) that has come back after standard treatment, such as Bacillus Calmette-Guerin (BCG) or chemotherapy instilled into the bladder. Participants in this study will have bladder cancer with a mutation in the FGFR3 gene. FGFR3 mutations are the most common genetic alteration in NMIBC and is present in the majority of recurrent NMIBC tumors. Genetic testing of the participant's prior or recurrent NMIBC tumor will be performed to confirm it has an FGFR3 gene mutation. Erdafitinib is a pill given orally (by mouth) that blocks the protein made by this altered gene, which may stop cancer cells from growing. Erdafitinib is already used as an approved treatment for metastatic bladder cancer. Researchers are doing this study to determine whether erdafitinib is an effective treatment for FGFR3-altered non-muscle invasive bladder cancer in the time period between when a recurrent tumor is identified and a TURBT (transurethral resection of a bladder tumor) or biopsy procedure is performed to remove it.

Will I have to stop taking my current medications?

The trial requires you to stop taking medications that increase phosphorus or calcium levels, as well as those that strongly or moderately affect certain liver enzymes (CYP3A4 or CYP2C9). If you're on these medications, you must discontinue them before starting erdafitinib.

Will I have to stop taking my current medications?

The trial requires you to stop taking medications that increase phosphorus or calcium levels, as well as those that strongly or moderately affect certain liver enzymes (CYP3A4 or CYP2C9). If you're on these medications, you must discontinue them before starting erdafitinib.

What data supports the effectiveness of the drug erdafitinib for bladder cancer?

Erdafitinib has been shown to be effective in stopping or reducing tumor growth in patients with advanced urothelial carcinoma, a type of bladder cancer, especially in those with specific genetic changes in FGFR2 and FGFR3 genes. It is approved for use in the USA for this condition and is being studied for other cancers as well. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Erdafitinib for bladder cancer?

Erdafitinib has been shown to be effective in stopping or reducing tumor growth in patients with advanced urothelial carcinoma, particularly those with specific genetic changes in FGFR2 and FGFR3 genes. It is approved for use in the USA for treating locally advanced or metastatic urothelial carcinoma, and studies have shown its potential in other cancers as well. ^{1 2 3 4 5}

Is erdafitinib safe for humans?

Erdafitinib, also known as Balversa, has been shown to be generally tolerable in patients with advanced bladder cancer, but it can cause side effects like high phosphate levels in the blood and eye problems, which require regular monitoring. ^{3 4 5 6 7}

Is erdafitinib safe for humans?

Erdafitinib, also known as Balversa, has been shown to be generally tolerable in patients with advanced bladder cancer, but it can cause side effects like high phosphate levels in the blood and eye problems, which require regular monitoring. ^{3 4 5 6 7}

What makes the drug erdafitinib unique for treating bladder cancer?

Erdafitinib is unique because it is the first oral drug approved for bladder cancer that specifically targets genetic changes in FGFR2 and FGFR3, which are often present in this type of cancer. It works by blocking these receptors, which can help stop or slow down tumor growth, offering a new option for patients who have not responded to other treatments. ^{1 3 4 8 9}

What makes the drug erdafitinib unique for treating bladder cancer?

Erdafitinib is unique because it is the first oral treatment specifically approved for bladder cancer with certain genetic changes (FGFR3/2 alterations), and it works by blocking proteins (FGFRs) that help cancer cells grow. This makes it different from other treatments that might not target these specific genetic changes. ^{3 4 8 9 10}

Research Team

Eugene Pietzak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with non-muscle invasive bladder cancer that has returned after treatments like BCG or chemo. Participants must have a specific FGFR3 gene mutation in their tumor, be able to perform daily activities, and have good organ function. Pregnant women, those with muscle-invasive or metastatic bladder cancer, and individuals on certain medications are excluded.

Inclusion Criteria

My bladder cancer has an FGFR3 mutation.

My bladder cancer has returned despite previous treatment.

Willing and able to provide written informed consent for the trial

Exclusion Criteria

I have been treated with a specific FGFR inhibitor before.

I have a bleeding or clotting disorder.

I have or am being treated for advanced bladder cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral erdafitinib to assess its effectiveness in treating FGFR3-altered non-muscle invasive bladder cancer

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Erdafitinib

Trial Overview The study tests the effectiveness of erdafitinib, an oral medication targeting a protein from the altered FGFR3 gene which may halt cancer cell growth. It's given to patients whose recurrent bladder tumors show this genetic change before they undergo surgery to remove the tumor.

Participant Groups

Group I: Participants with FGFR3-mutant or -fusion noninvasive bladder tumors Experimental Treatment 1 Intervention

25 participants with FGFR3-mutant or -fusion noninvasive bladder tumors will be accrued.

Erdafitinib is already approved in United States, European Union for the following indications:

Approved in United States as Balversa for:

• Locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations

Approved in European Union as Balversa for:

• Locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In the BLC2001 study involving 212 participants with advanced urothelial carcinoma, 40% of those treated with an 8 mg daily dose of erdafitinib experienced a reduction in tumor size or complete disappearance of tumors, indicating its efficacy in this difficult-to-treat cancer.

Approximately 80% of participants achieved disease control, meaning their tumors either shrank or remained stable, with an estimated 55% survival rate after one year and 31% after two years, highlighting the potential of erdafitinib as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary of erdafitinib in locally advanced or metastatic urothelial carcinoma: a phase 2 study with long-term follow-up. Loriot, Y., O'Hagan, A., Siefker-Radtke, AO.[2023]

In a study involving 73 patients with high-risk non-muscle-invasive bladder cancer (NMIBC) who had recurrence after BCG treatment, oral erdafitinib significantly prolonged recurrence-free survival (RFS) compared to intravesical chemotherapy, with a median RFS not reached for erdafitinib versus 11.6 months for chemotherapy.

The safety profile of erdafitinib was consistent with known effects, indicating it is a viable treatment option for patients with specific FGFR alterations who are ineligible for or refuse radical cystectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib in BCG-treated high-risk non-muscle invasive bladder cancer. Catto, JWF., Tran, B., Rouprêt, M., et al.[2023]

Erdafitinib, a tyrosine kinase inhibitor for advanced urothelial carcinoma, was studied using a pharmacokinetic model in mice and rats to determine effective dosing for phase 1 trials, showing that doses above 4 mg/day resulted in significant tumor growth inhibition.

The modeling predicted that efficacious unbound concentrations of erdafitinib were identified, aligning with early clinical activity observed at a dose of 6 mg in the first-in-human trial, demonstrating the potential of translational modeling in optimizing drug dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A translational model-based approach to inform the choice of the dose in phase 1 oncology trials: the case study of erdafitinib. Tosca, EM., Terranova, N., Stuyckens, K., et al.[2022]

Erdafitinib is a newly approved pan-FGFR inhibitor specifically for treating locally advanced or metastatic urothelial carcinoma associated with FGFR3 or FGFR2 mutations.

The drug is also being explored for its potential effectiveness against various other cancers, including cholangiocarcinoma and non-small cell lung cancer, indicating its broad therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib: First Global Approval. Markham, A.[2020]

A 58-year-old man developed blurry vision and secondary maculopathy after 3 weeks of treatment with erdafitinib for bladder cancer, indicating potential ocular toxicity associated with this medication.

Discontinuation of erdafitinib led to improvements in both vision and eye health, highlighting the need for monitoring ocular side effects in patients receiving FGFR inhibitors like erdafitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib-Induced Secondary Maculopathy. Becker, B., El Hamichi, S., Gold, AS., et al.[2023]

In a long-term follow-up of the BLC2001 study involving 101 patients with advanced urothelial carcinoma, erdafitinib demonstrated a 40% objective response rate, indicating its efficacy in this patient population with specific FGFR alterations.

The safety profile of erdafitinib remained consistent over time, with 71% of patients experiencing grade 3-4 adverse events, but no new safety concerns were identified, suggesting it is a manageable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Siefker-Radtke, AO., Necchi, A., Park, SH., et al.[2022]

Erdafitinib is the first targeted therapy approved by the FDA for metastatic bladder cancer, showing a 40% overall response rate in the BLC2001 trial for patients with specific FGFR genetic alterations.

While effective, erdafitinib can cause side effects like hyperphosphatemia and retinopathy, necessitating regular monitoring, and further research is needed to optimize its use alongside other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evidence and Selecting Patients for Treatment with Erdafitinib in Advanced Urothelial Carcinoma. Sayegh, N., Tripathi, N., Agarwal, N., et al.[2022]

Erdafitinib is the first FDA-approved oral medication that targets multiple fibroblast growth factor receptors (FGFR-1 to -4), leading to reduced cell signaling and increased cancer cell death, making it a novel treatment for urothelial carcinoma.

This drug is specifically approved for adult patients with advanced urothelial carcinoma who have certain genetic alterations in FGFR3 or FGFR2 and have not responded to previous platinum-based chemotherapy, providing a new option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib to treat urothelial carcinoma. Hanna, KS.[2019]

In a phase III study involving 351 patients with metastatic urothelial carcinoma, erdafitinib and pembrolizumab showed similar overall survival rates, with median survival times of 10.9 months and 11.1 months, respectively.

Erdafitinib demonstrated a higher objective response rate (40.0% vs. 21.6%) compared to pembrolizumab, although the duration of response was shorter for erdafitinib (4.3 months vs. 14.4 months), indicating that while erdafitinib may lead to more immediate responses, pembrolizumab may provide longer-lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial. Siefker-Radtke, AO., Matsubara, N., Park, SH., et al.[2023]

In a phase 3 trial involving 266 patients with metastatic urothelial carcinoma and FGFR alterations, erdafitinib significantly improved overall survival compared to chemotherapy, with a median survival of 12.1 months versus 7.8 months.

Erdafitinib also demonstrated a longer median progression-free survival of 5.6 months compared to 2.7 months for chemotherapy, while having a similar incidence of severe treatment-related adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. Loriot, Y., Matsubara, N., Park, SH., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Plain language summary of erdafitinib in locally advanced or metastatic urothelial carcinoma: a phase 2 study with long-term follow-up. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Erdafitinib in BCG-treated high-risk non-muscle invasive bladder cancer. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

A translational model-based approach to inform the choice of the dose in phase 1 oncology trials: the case study of erdafitinib. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Erdafitinib: First Global Approval. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Erdafitinib-Induced Secondary Maculopathy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Evidence and Selecting Patients for Treatment with Erdafitinib in Advanced Urothelial Carcinoma. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

Erdafitinib to treat urothelial carcinoma. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. [2023]