Erdafitinib vs Chemotherapy for Bladder Cancer

Recruiting at 188 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: FGFR inhibitors

Disqualifiers: Muscle-invasive cancer, Small cell, 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: 1

Duration: Up to 4 years

107 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests erdafitinib, a pill that targets proteins to stop cancer growth, in patients with a type of bladder cancer that has returned after standard treatment. The drug blocks signals that help cancer cells grow. Erdafitinib is approved for treating a specific type of advanced bladder cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Erdafitinib has been shown to be effective in treating advanced bladder cancer, particularly in patients with specific genetic changes (FGFR2 and FGFR3 alterations), by stopping or reducing tumor growth. It is approved for use in patients whose cancer has progressed after other treatments, like chemotherapy. ^{1 2 3 4 5}

Is erdafitinib safe for humans?

Erdafitinib has been shown to be generally tolerable in patients with advanced bladder cancer, but common side effects include high phosphate levels in the blood and eye problems, which require regular monitoring. ^{1 2 3 6 7}

How is the drug erdafitinib different from other treatments for bladder cancer?

Erdafitinib is unique because it is an oral drug that specifically targets and inhibits fibroblast growth factor receptors (FGFRs), which are often altered in certain bladder cancers. This makes it particularly effective for patients with FGFR3 or FGFR2 alterations, offering a targeted approach compared to traditional chemotherapy. ^{1 2 3 8 9}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with high-risk non-muscle-invasive bladder cancer that has returned after BCG therapy. Participants must have specific FGFR mutations or fusions, be unable to undergo cystectomy, and have good performance status (ECOG 0-1). They need proper organ function and a negative pregnancy test for women of childbearing potential.

Inclusion Criteria

I am not undergoing or cannot undergo bladder removal surgery.

Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study

I am fully active or can carry out light work.

Exclusion Criteria

I have no active cancers except possibly treated skin cancer, certain breast or prostate cancers.

My bladder cancer is a specific type, like small cell or squamous.

I have been treated with an FGFR inhibitor before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either erdafitinib or investigator's choice of intravesical chemotherapy

Up to 4 years

Cycle 1 Day 14, Cycle 2 Day 1 (each cycle is of 28 days)

Follow-up

Participants are monitored for recurrence-free survival and adverse events

Up to 4 years

Long-term extension

Participants may continue treatment with erdafitinib if they demonstrate recurrence

Treatment Details

Interventions

• Erdafitinib
• Gemcitabine
• Mitomycin C

Trial Overview The study compares the effectiveness of Erdafitinib against standard intravesical chemotherapy drugs like Gemcitabine or Mitomycin C in preventing cancer recurrence. It targets patients whose bladder cancer harbors certain genetic changes and who didn't respond well to previous treatments.

Participant Groups

Group I: Cohort 3 Experimental Treatment 1 Intervention

Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.

Group II: Cohort 2 Experimental Treatment 1 Intervention

Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.

Group III: Cohort 1: Erdafitinib Experimental Treatment 1 Intervention

Participants with high-risk non-muscle-invasive bladder cancer (NMIBC) presenting as papillary tumor only (carcinoma in situ \[CIS\], absent), with disease recurrence after bacillus Calmette- Guerin (BCG) therapy will receive treatment with erdafitinib.

Group IV: Cohort 1: Investigators Choice Active Control 2 Interventions

Participants with high-risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy will receive the investigator's choice of either intravesical gemcitabine or intravesical mitomycin C (MMC) or hyperthermic MMC. Participants who are randomized to gemcitabine or MMC or hyperthermic MMC in Cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib.

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?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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 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]

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]

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 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 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 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]

References

1. 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]

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

Erdafitinib: First Global Approval. [2020]

3. 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]

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

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

5. 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]

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

Erdafitinib-Induced Secondary Maculopathy. [2023]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

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]