Erdafitinib Delivery System for Bladder Cancer

Recruiting at 76 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering the drug Erdafitinib (also known as Balversa or JNJ-42756493) directly to the bladder to treat non-muscle invasive bladder cancer, where cancer cells remain in the bladder's inner lining. The trial aims to determine the right dose, assess safety, and evaluate effectiveness. It progresses in stages, starting with dose determination and advancing to effectiveness and safety testing. Individuals with recurrent bladder cancer or cancer that does not penetrate deeply into the bladder wall may qualify, particularly if their cancer exhibits certain genetic changes. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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 prior data suggests that the Erdafitinib Intravesical Delivery System is safe for bladder cancer treatment?

Research has shown that the Erdafitinib Intravesical Delivery System has been generally safe in past studies. Most side effects are mild and primarily affect the urinary system, causing discomfort or irritation. This treatment delivers medication directly into the bladder, helping to prevent side effects in other parts of the body. Due to this targeted approach, fewer serious problems have been reported. Overall, the safety data appears promising, but further research is underway to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bladder cancer?

Unlike the standard of care for bladder cancer, which often involves systemic therapies or surgeries, Erdafitinib is delivered directly into the bladder using an intravesical delivery system. This localized delivery helps target the cancer cells more directly, potentially reducing side effects associated with systemic treatments. Erdafitinib works by inhibiting FGFR (fibroblast growth factor receptors), a pathway that can promote cancer cell growth, offering a novel mechanism of action compared to traditional options. Researchers are excited about this approach because it could offer a more effective and patient-friendly treatment option for those with non-muscle-invasive bladder cancer.

What evidence suggests that the Erdafitinib Intravesical Delivery System might be an effective treatment for bladder cancer?

Research has shown that the Erdafitinib Intravesical Delivery System holds promise for treating non-muscle invasive bladder cancer (NMIBC). Early results are particularly positive for patients with specific gene changes related to the fibroblast growth factor receptor (FGFR). In this trial, participants will receive Erdafitinib in various phases, including dose escalation and expansion, to assess its safety and efficacy. Recent data indicates that many patients showed early signs of improvement. Specifically, another study found that 94% of participants continued the treatment for an average of 3.7 months. This suggests the treatment is effective and well-tolerated, offering hope for those with this type of bladder cancer. ^{2 4 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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, 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05316155

NCT05316155 | Study of Erdafitinib Intravesical Delivery ... The study consists of a screening phase, a treatment phase, and a follow-up phase. Total duration of the study is 5 years 11 months.

2. clinicaltrial.be clinicaltrial.be/en/details/14316?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

A Study of Erdafitinib Intravesical Delivery System in Ja... Confirmed recurrence of non-muscle invasive bladder cancer (NMIBC) after prior therapy that meet either one: a. Recurrence of high-risk NMIBC ...

3. jnj.com jnj.com/media-center/press-releases/first-results-with-erdafitinib-releasing-intravesical-delivery-system-tar-210-show-early-evidence-of-positive-clinical-activity-in-patients-with-non-muscle-invasive-bladder-cancer-with-select-fibroblast-growth-factor-receptor-alterations

First Results with Erdafitinib-Releasing Intravesical ... Median duration of treatment exposure was 3.7 months, with 94 percent of the 16 patients still on study. In C3, 87 percent of the 27 patients ...

4. 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

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

5. urotoday.com urotoday.com/conference-highlights/eau-2024/eau-2024-bladder-cancer/151001-eau-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

First Safety and Efficacy Results of the TAR-210 Erdafitinib ... TAR-210 shows promising clinical activity in patients with FGFR-altered high-risk and intermediate-risk non-muscle invasive bladder cancer with ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04274-6/fulltext

LBA104 First safety and efficacy results of the TAR-210 ... TAR-210 appears safe and well tolerated with predominantly low-grade urinary system AEs and high CR rate and RF survival in pts with NMIBC with FGFRalt. Results ...

7. auajournals.org auajournals.org/doi/10.1097/01.JU.0001008712.53259.7d.02

PD48-02 FIRST SAFETY AND EFFICACY RESULTS OF ... CONCLUSIONS: TAR-210 appears safe and well tolerated with predominantly low-grade urinary system TRAEs and high CR rate and RF survival in ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT394836

Safety and efficacy of the erdafitinib (erda) intravesical ... TAR-210 is an intravesical drug delivery system designed to provide local, continuous release of erda within the bladder, thus limiting systemic toxicity.