Erdafitinib Combo for Bladder Cancer

Not currently recruiting at 209 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Nitrosoureas, Mitomycin C, PD-1 inhibitors

Disqualifiers: Active malignancies, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new combinations of medicines for advanced bladder cancer. It aims to determine a safe and effective dose of erdafitinib (Balversa, a targeted therapy) when combined with other drugs, such as cetrelimab (an experimental treatment) and certain chemotherapy drugs. The trial seeks participants with advanced or metastatic bladder cancer who have not received prior treatment for metastatic disease. It specifically targets those with specific changes in the FGFR gene, which may influence cancer growth. Participants must have a diagnosis of advanced bladder cancer and measurable disease visible on scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken other investigational drugs or certain chemotherapies recently. It's best to discuss your current medications with the trial team.

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

Research shows that erdafitinib, when used alone, effectively treats urothelial cancer, a type of bladder cancer. The European Medicines Agency has already approved it for this use. In earlier studies, common side effects included high phosphate levels in the blood, mouth sores, diarrhea, dry mouth, and changes in taste.

When combined with cetrelimab, studies have found erdafitinib to be generally well-tolerated and beneficial. Cetrelimab, a PD-1 inhibitor, helps the immune system fight cancer. It has been tested in several trials and has shown a solid safety record.

The safety of combining erdafitinib, cetrelimab, and platinum-based chemotherapy (cisplatin or carboplatin) is still under study. These combinations are being tested to determine the best dose and schedule. This phase of the trial is crucial for understanding patient tolerance and potential side effects. Overall, the treatments appear promising, but the ongoing study will provide clearer safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of erdafitinib and cetrelimab for bladder cancer because it targets cancer differently than current standard treatments. Most treatments, like chemotherapy, broadly attack fast-growing cells. Erdafitinib, however, is a fibroblast growth factor receptor (FGFR) inhibitor, which specifically targets genetic alterations in cancer cells, potentially leading to more effective and personalized treatment. Additionally, cetrelimab is an immune checkpoint inhibitor that helps the immune system recognize and fight cancer cells. This combination not only aims to target the cancer more precisely but also enhances the body's immune response against it, offering a promising new approach compared to traditional therapies.

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

Research has shown that erdafitinib can effectively treat advanced bladder cancer, particularly in patients with specific FGFR gene changes. One study found that patients taking erdafitinib lived an average of 12.1 months, compared to 7.8 months for those receiving chemotherapy. In this trial, participants will receive erdafitinib alone or with cetrelimab, which has demonstrated a better response rate, with 68% of patients responding compared to 33% with erdafitinib alone. Additionally, some participants will receive a combination of erdafitinib, cetrelimab, and platinum-based chemotherapy (cisplatin or carboplatin), which might further improve survival. Erdafitinib has already been shown to reduce the risk of death by 36% in some studies. These findings suggest that these treatments could be promising for bladder cancer patients with certain genetic profiles. ^{1 6 7 8 9}

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 advanced or metastatic urothelial cancer, specifically transitional cell carcinoma. Participants must have measurable disease and no prior systemic therapy for metastatic disease (or are cisplatin-ineligible). They should not have received certain treatments recently and must have adequate kidney function.

Inclusion Criteria

Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2

Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2

My bladder cancer has been confirmed by a biopsy.

Exclusion Criteria

I am not receiving treatment for any cancer other than urothelial cancer.

I've had previous treatments targeting PD-1, PD-L1, or PD-L2, but stopped over a year ago without severe side effects.

I have symptoms from cancer spread to my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1b: Dose Escalation

Participants receive erdafitinib orally followed by cetrelimab intravenously and carboplatin/cisplatin IV as a part of platinum chemotherapy. Dose levels are escalated sequentially until the recommended Phase 2 Dose (RP2D) is identified.

Up to 8 weeks

Treatment Phase 2: Dose Expansion

Participants are randomized to receive either erdafitinib alone or the identified RP2D of erdafitinib in combination with cetrelimab.

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cetrelimab
• Cisplatin
• Erdafitinib

Trial Overview

The study tests the safety, tolerability, and optimal dosing of erdafitinib alone or combined with cetrelimab and platinum-based chemotherapy (cisplatin or carboplatin) in patients. It aims to find the best dose for Phase 2 trials and assess how well these combinations work against this type of cancer.

How Is the Trial Designed?

Group I: Phase 2: Dose Expansion Experimental Treatment 2 Interventions

The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV).

Group II: Phase 1b: Dose Escalation Experimental Treatment 4 Interventions

Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.

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

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]

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, 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 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 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]

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]

Citations

1.

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 ...

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fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-erdafitinib-locally-advanced-or-metastatic-urothelial-carcinoma

FDA approves erdafitinib for urothelial carcinoma

Median OS was 12.1 months (95% CI: 10.3, 16.4) for patients who received erdafitinib and 7.8 months (95% CI: 6.5, 11.1) for those who received ...

3.

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 ...

Treatment with BALVERSA® also showed an improvement in median PFS compared to chemotherapy of 5.6 months versus 2.7 months (HR 0.58; [95 percent ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10244774/

Erdafitinib treatment in metastatic urothelial carcinoma

Erdafitinib treatment outcomes. Median follow–up time was 24 months (range 13–30 months). A clinical benefit was seen in 56% (n=15) ...

5.

jheor.org

jheor.org/article/120954-matching-adjusted-indirect-comparison-of-the-efficacy-and-safety-of-erdafitinib-vs-enfortumab-vedotin-in-patients-with-locally-advanced-metastatic-uro

Matching-Adjusted Indirect Comparison of the Efficacy and ...

The cCR rate of erdafitinib improved minimally from 3.4% to 3.6%, whereas the cCR rate for chemotherapy decreased from 1.3% to 0.7%; Table 3).

6.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/balversa

Balversa | European Medicines Agency (EMA)

Balversa is used to treat urothelial cancer (cancer of the bladder and urinary system) in adults. It is used on its own when the cancer is unresectable.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10702547/

Adverse events in patients with advanced urothelial ...

The most common AEs observed in the BLC2001 study included hyperphosphatemia (78%), stomatitis (35%), diarrhea (54%), nausea (22%), dry mouth (46%), dysgeusia ( ...

8.

mayoclinic.org

mayoclinic.org/drugs-supplements/erdafitinib-oral-route/description/drg-20461324

Erdafitinib (oral route) - Side effects & dosage

Erdafitinib is used to treat urothelial carcinoma (bladder cancer) that has spread or cannot be removed by surgery. ... Safety and efficacy ...

9.

balversahcp.com

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

Mechanism of Action - BALVERSA™ (erdafitinib) HCP

The safety population described in the Warnings and Precautions reflect a pooled safety population of 479 patients with advanced urothelial cancer and FGFR ...