Erdafitinib Delivery System for Bladder Cancer

Recruiting at 34 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: FGFR inhibitors

Disqualifiers: Concurrent extra-vesical carcinoma, others

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

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

262 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new way to deliver a drug called Erdafitinib directly into the bladder for patients with certain types of bladder cancer. These patients have genetic changes that make their cancer harder to treat. The drug works by blocking proteins that help the cancer grow. The goal is to find the best dose and see how well it works and how safe it is.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have received an investigational treatment for bladder cancer recently, you may need to wait for a certain period before starting the study treatment.

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

Erdafitinib has been approved for treating advanced urothelial carcinoma, a type of bladder cancer, based on studies showing its ability to target specific genetic changes in cancer cells, leading to tumor shrinkage. It works by blocking certain proteins (FGFRs) that help cancer cells grow, and has shown significant activity in patients with these genetic alterations. ^{1 2 3 4 5}

Is erdafitinib safe for humans?

Erdafitinib has been shown to be generally tolerable in patients with advanced urothelial carcinoma, but it can cause side effects like secondary maculopathy (an eye condition). It has been studied in various cancers, and safety data from these studies suggest it is safe for human use with monitoring for side effects. ^{1 2 3 5 6}

What makes the Erdafitinib Delivery System unique for bladder cancer treatment?

The Erdafitinib Delivery System is unique because it delivers the drug directly into the bladder, which may enhance its effectiveness and reduce side effects compared to traditional oral administration. This method targets the cancer more precisely, potentially improving outcomes for patients with specific genetic alterations in their tumors. ^{1 2 3 5 7}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for people with recurrent bladder cancer that hasn't spread into muscle or has just started to. They must have a specific genetic change in their tumor and may or may not have had BCG therapy, depending on the group they're placed in. Surgery should be an option for some participants. Those who've had recent pelvic radiation, certain bladder conditions, permanent urinary catheters, or previous FGFR inhibitor treatments can't join.

Inclusion Criteria

My bladder cancer has grown into the muscle or has come back but not in the muscle.

I am willing and meet the requirements for radical cystectomy.

I have either been treated with BCG, couldn't get it due to unavailability, or stopped it early due to side effects.

Exclusion Criteria

I use a catheter for urination.

I have bladder cancer that has spread to nearby organs.

Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe use of Erdafitinib intravesical delivery system

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of Erdafitinib to determine the recommended Phase 2 dose(s) (RP2D)

28 days

Dose Expansion

Participants are enrolled in disease-specific cohorts to evaluate safety, efficacy, and pharmacokinetics at the RP2D

6 months

RP2D Expansion

Participants with intermediate-risk non-muscle invasive bladder cancer are assessed for overall complete response at the RP2D

5 years 11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years 11 months

Treatment Details

Interventions

• Erdafitinib Intravesical Delivery System

Trial Overview The study is testing Erdafitinib Intravesical Delivery System directly applied inside the bladder. The first part of the trial will find the best dose to use while the second part checks how safe it is at that dose.

Participant Groups

Group I: Part 4: Phase 2 Expansion Experimental Treatment 1 Intervention

Participants with recurrent IR-NMIBC will be enrolled in this part to further evaluate the safety, efficacy, and PK of the selected RP2D.

Group II: Part 3: RP2D Dose Expansion Experimental Treatment 1 Intervention

Participants in 2 of the disease-specific NMIBC cohorts (cohorts 1 and 3) may be enrolled at RP2D to determine the safety, evaluate PK and preliminary clinical activity.

Group III: Part 2: Dose Expansion Experimental Treatment 1 Intervention

Participants in each of 5 disease-specific NMIBC or MIBC cohorts may be enrolled at one or more dose levels that have been determined to be safe in Part 1.

Group IV: Part 1: Dose Escalation Experimental Treatment 1 Intervention

Participants with recurrent, bacillus Calmette-Guerin (BCG)-experienced high risk papillary-only Non-Muscle-Invasive Bladder Cancer (NMIBC), refusing or ineligible for radical cystectomy or with recurrent, intermediate-risk NMIBC will receive Erdafitinib Intravesical Delivery System. The dose will be escalated to determine preliminary recommended phase 2 dose(s) (RP2D\[s\]) for Part 2.

Erdafitinib Intravesical Delivery System is already approved in United States for the following indications:

Approved in United States as Balversa for:

• Locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 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]

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]

Erdafitinib, a targeted therapy for metastatic urothelial carcinoma (mUC), showed promising efficacy in a real-world setting, with 33% of patients experiencing a partial response and a median time to treatment failure of 5.3 months for those with an objective response.

The treatment was generally well-tolerated, although 83% of patients reported adverse events, with hyperphosphatemia being the most common, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib treatment in Brazilian patients with metastatic urothelial carcinoma (mUC): real-world evidence from an Expanded Access Program. Monteiro, FSM., Silva, AGE., Gomes, AJPS., 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]

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

Erdafitinib-Induced Secondary Maculopathy. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

Erdafitinib to treat urothelial carcinoma. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Erdafitinib treatment in Brazilian patients with metastatic urothelial carcinoma (mUC): real-world evidence from an Expanded Access Program. [2022]

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. 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]