Oral Erdafitinib for Bladder Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of an oral medication called erdafitinib (Balversa) for treating non-muscle invasive bladder cancer (NMIBC) that has returned after standard treatments like BCG or chemotherapy. Erdafitinib blocks a specific protein in cancer cells, potentially stopping cancer growth. The trial targets individuals whose bladder cancer has a mutation in the FGFR3 gene, a common change in recurring NMIBC. Candidates should have experienced NMIBC recurrence after previous treatments and be able to continue with daily activities. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that erdafitinib is likely to be safe for humans?

Research has shown that erdafitinib, a drug approved for advanced bladder cancer, has some safety information available. In studies, about 46% of patients experienced serious side effects, known as grade three or higher treatment-related adverse events. These serious side effects can include severe tiredness, nausea, or vision changes.

However, the overall safety of erdafitinib is similar to that of chemotherapy. While possible side effects exist, they are not necessarily worse than those from other cancer treatments. Recent studies found no new safety issues, which is reassuring for those considering this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Erdafitinib is unique because it specifically targets FGFR3 mutations or fusions found in certain bladder tumors. Unlike standard treatments like chemotherapy or immune checkpoint inhibitors, erdafitinib works by inhibiting the fibroblast growth factor receptor pathways, which can be a driving force in tumor growth. This targeted approach not only aims to be more effective for these specific genetic alterations but also may result in fewer side effects compared to broader, less targeted therapies. Researchers are excited about erdafitinib because it offers a personalized treatment option that could potentially improve outcomes for patients with these genetic profiles.

What evidence suggests that erdafitinib might be an effective treatment for non-muscle invasive bladder cancer?

Research has shown that erdafitinib is effective against bladder cancer with certain genetic changes. It works well for patients with FGFR3 gene mutations, often found in bladder cancer that returns after standard treatments. Erdafitinib blocks a protein produced by this altered gene, potentially stopping cancer cell growth. It is already approved for treating bladder cancer that has spread to other parts of the body. In this trial, participants with FGFR3-mutant or -fusion noninvasive bladder tumors will receive erdafitinib, suggesting it could also help with non-muscle invasive bladder cancer (NMIBC) when the cancer recurs after other treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

Eugene Pietzak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308849

Erdafitinib or Chemotherapy in Advanced or Metastatic ... The possible overall survival benefit that was observed with erdafitinib in patients with upper tract urothelial cancer may be clinically ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16571

Efficacy of erdafitinib in FGFR2/3-altered metastatic ... Efficacy of erdafitinib in FGFR2/3-altered metastatic urothelial cancer ... bladder cancer (UBC). Maroun Bou Zerdan et al. +0 authors.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11233068/

Clinical and genomic landscape of FGFR3-altered urothelial ... Erdafitinib is the only FDA-approved targeted therapy for FGFR2/3-altered metastatic urothelial cancer. We characterized the genetic landscape of FGFR-altered ...

4. jnj.com jnj.com/innovativemedicine/emea/newsroom/oncology/chmp-adopts-positive-opinion-for-balversa-erdafitinib-for-the-treatment-of-adult-patients-with-unresectable-or-metastatic-urothelial-carcinoma-with-susceptible-fgfr3-genetic-alterations

CHMP adopts positive opinion for BALVERSA® (erdafitinib ... The five-year survival rate for patients with metastatic bladder cancer that has spread to distant parts of the body is currently 8 percent.26. About FGFR ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2019/erdafitinib-advanced-bladder-cancer

Erdafitinib Effective Against Advanced Bladder Cancer - NCI The updated results confirm that erdafitinib can benefit patients with advanced bladder cancer whose tumors have a genetic alteration in one ...

6. jnj.com jnj.com/media-center/press-releases/janssen-announces-balversa-erdafitinib-improved-overall-survival-versus-chemotherapy-in-patients-with-metastatic-or-unresectable-urothelial-carcinoma-and-selected-fibroblast-growth-factor-receptor-gene-alterations-after-prior-anti-pd-l1-treatment

Janssen Announces BALVERSA® (erdafitinib) Improved ... Grade three or higher TRAEs were observed in 45.5 percent of patients who received BALVERSA® and cetrelimab combination therapy and 46.5 percent ...

7. balversahcp.com balversahcp.com/clinical-information/mechanism-of-action

Mechanism of Action - BALVERSA™ (erdafitinib) HCP BALVERSA® demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer. 1. BALVERSA® ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/n/ht8269678067037582/

Erdafitinib (Balversa) - NCBI Bookshelf - NIH Other AEs and the overall safety profile were comparable between erdafitinib and chemotherapy. ... erdafitinib to other patients with bladder cancer.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.17_suppl.LBA4619

Phase 3 THOR study: Results of erdafitinib (erda) versus ... No new safety signals were seen. Serious treatment-related adverse events (TRAEs) were observed in 13% and 24% of pts with erda and chemo, ...