Erdafitinib vs Chemotherapy for Bladder Cancer

No longer recruiting at 237 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called erdafitinib (Balversa) for individuals with bladder cancer that has returned after standard treatment. Researchers aim to determine if erdafitinib can prevent cancer recurrence more effectively than other treatments like chemotherapy. Participants are divided into groups, with some receiving erdafitinib and others receiving chemotherapy options selected by their doctor. Suitable candidates have bladder cancer that hasn't spread to muscle, possess specific gene changes (FGFR mutations), and have not responded to a therapy called BCG. As a Phase 2 trial, this research measures erdafitinib's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that erdafitinib is generally well-tolerated by patients with bladder cancer. One study found that patients with advanced bladder cancer lived longer on erdafitinib than those receiving chemotherapy, suggesting its effectiveness and safety.

An independent committee reviewed erdafitinib's safety in early patients and recommended some changes, indicating careful safety monitoring. Additionally, erdafitinib is being tested in new ways, such as direct administration into the bladder, which has shown promising safety results.

Overall, despite some adjustments and ongoing monitoring, erdafitinib has demonstrated a safety profile that supports its continued study in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Erdafitinib is unique because it specifically targets the fibroblast growth factor receptor (FGFR) pathway, which is often altered in bladder cancer. Unlike standard treatments like intravesical chemotherapy, which involves administering drugs directly into the bladder, erdafitinib is an oral medication, offering a more convenient option for patients. Researchers are excited about this treatment because it provides a more targeted approach, potentially leading to better outcomes for patients with specific genetic mutations related to bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that erdafitinib may effectively treat bladder cancer, particularly in patients with specific genetic changes in their tumors. In this trial, some participants will receive erdafitinib, which previous studies found helped patients with advanced bladder cancer live longer compared to traditional chemotherapy. For patients with non-muscle-invasive bladder cancer, 90% did not experience a recurrence, meaning the cancer stayed away for most. Additionally, 90% of patients had no detectable cancer after treatment. These results suggest erdafitinib could be a viable option for those unresponsive to other treatments. Meanwhile, other participants in this trial will receive the investigator's choice of either intravesical gemcitabine, mitomycin C, or hyperthermic mitomycin C as part of the chemotherapy arm. ^{1 2 4 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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, 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]

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]

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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0302283825047025

Erdafitinib in Patients with High- and Intermediate-risk Non ... This final analysis of the multicohort phase 2 THOR-2 trial shows that oral erdafitinib achieved superior recurrence-free survival compared with ...

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

Erdafitinib or Chemotherapy in Advanced or Metastatic ... Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR ...

3. urotoday.com urotoday.com/conference-highlights/aua-2024/aua-2024-bladder-cancer/151853-aua-2024-first-safety-and-efficacy-results-of-the-tar-210-erdafitinib-intravesical-delivery-system-in-patients-with-non-muscle-invasive-bladder-cancer-with-select-fgfr-alterations.html

AUA 2024: First Safety and Efficacy Results of the TAR-210 ... Dr. Antoni Vilaseca presented presented the first safety and efficacy results of the TAR-210 erdafitinib intravesical delivery system in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12439848/

Targeted Therapy in Non-Muscle Invasive Bladder Cancer ... In this trial of 608 patients, risk of death was reduced by 30% in the EV arm compared to chemotherapy (hazard ratio (HR) 0.70, 95% confidence interval [CI] ...

5. jnj.com jnj.com/media-center/press-releases/tar-210-results-show-90-recurrence-free-survival-and-90-complete-response-in-patients-with-high-risk-and-intermediate-risk-non-muscle-invasive-bladder-cancer-respectively

TAR-210 results show 90% recurrence-free survival and ... TAR-210 results show 90% recurrence-free survival and 90% complete response in patients with high-risk and intermediate-risk non–muscle-invasive bladder cancer ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04015-2/fulltext

Erdafitinib in BCG-treated high-risk non-muscle-invasive ... The independent data monitoring committee reviewed safety data from the first four patients treated with erdafitinib and recommended changing ...