Erdafitinib for Bladder Cancer

(THOR Trial)

Not currently recruiting at 529 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: FGFR inhibitors

Disqualifiers: Active malignancies, CNS metastases, cardiovascular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, erdafitinib, for individuals with advanced bladder cancer. It compares the effectiveness of erdafitinib against traditional treatments like chemotherapy and pembrolizumab, an immune therapy drug. The trial targets those whose cancer has worsened after one or two treatments, including those who have already tried immune therapy. Ideal participants have bladder cancer that has spread or cannot be surgically removed and have experienced cancer progression after previous treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken another investigational agent within 30 days before the trial.

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

In a previous study, erdafitinib helped patients with urothelial carcinoma, a type of bladder cancer, live longer. Most patients tolerated it well, though some experienced side effects like high phosphate levels in their blood. Its approval for similar conditions supports its safety.

Vinflunine is another treatment under testing. Research has indicated its safety for bladder cancer, though some patients reported side effects like nausea and vomiting. It is approved in Europe for bladder cancer when other treatments have failed.

Docetaxel, a chemotherapy drug, can be safely used even with kidney problems. It is approved for certain cancers and is generally well-tolerated.

Pembrolizumab, an immunotherapy drug, helps the immune system fight cancer and is FDA-approved for advanced bladder cancer. Some patients have experienced serious side effects like infections and lung issues, but these are managed in trials.

Each treatment has different side effects, so discussing options with a doctor is important to determine the best choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about erdafitinib for bladder cancer because it targets the fibroblast growth factor receptor (FGFR) pathway, which is a novel approach compared to the standard chemotherapy options like cisplatin and gemcitabine. Unlike traditional chemotherapy that attacks rapidly dividing cells in general, erdafitinib specifically hones in on cancer cells with FGFR mutations, potentially leading to more effective and targeted treatment. This precision could mean fewer side effects and improved outcomes for patients with these specific genetic markers. Additionally, erdafitinib is taken orally, providing a more convenient alternative to the intravenous administration required for many chemotherapy treatments.

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

This trial will evaluate different treatments for advanced bladder cancer. Studies have shown that erdafitinib, which participants in this trial may receive, is effective for advanced bladder cancer with specific genetic changes. Patients taking erdafitinib lived for a median of 12.1 months, compared to 7.8 months for those on chemotherapy. Another treatment option in this trial is vinflunine, which research indicates offers some benefit for those with metastatic bladder cancer, with a median survival of about 6.9 months. Docetaxel, also part of this trial, has shown modest results, with patients experiencing a median time of 2.8 months before the cancer worsens. Pembrolizumab, another treatment arm in this trial, has been found to extend survival by about three months compared to chemotherapy in advanced cases. These treatments offer different benefits depending on individual patient factors. ^{1 2 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 adults with advanced bladder cancer that has worsened after treatment. Participants must have specific FGFR gene changes, and can join one of two groups: those who've had up to two treatments including an anti-PD-(L)1 drug, or those who've had just one prior treatment without an anti-PD-(L)1 drug. They should be relatively healthy otherwise and not pregnant if they're women of childbearing age.

Inclusion Criteria

Documented progression of disease prior to randomization

Negative pregnancy test for sexually active women of childbearing potential at Screening

My bladder cancer has spread or cannot be removed by surgery.

Exclusion Criteria

Treatment with any other investigational agent within 30 days prior to randomization

I am not allergic to erdafitinib or its ingredients.

I have a history of heart disease that is not well-controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive erdafitinib, vinflunine, docetaxel, or pembrolizumab based on cohort assignment until disease progression, intolerable toxicity, or withdrawal

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3 years

Long-term Extension

Participants may continue to receive the study drug if they benefit from the treatment, as per investigator's decision

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Erdafitinib
• Pembrolizumab
• Vinflunine

Trial Overview The study compares the effectiveness of a new medication called Erdafitinib against either chemotherapy drugs Vinflunine or Docetaxel, or immunotherapy Pembrolizumab in patients whose bladder cancer has specific genetic markers and has progressed despite previous treatments.

How Is the Trial Designed?

Group I: Cohort 2 (Arm 2B): Pembrolizumab Experimental Treatment 2 Interventions

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive the pembrolizumab until 2 years after the first dose of pembrolizumab (at start of study) or until the participant can commercially receive pembrolizumab within the local healthcare system, whichever comes first.

Group II: Cohort 2 (Arm 2A): Erdafitinib Experimental Treatment 2 Interventions

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 mg, once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on phosphate level and observed toxicity (AEs). Participants who enter in LTE phase will continue to receive the erdafitinib tablet as per investigator's decision.

Group III: Cohort 1 (Arm 1B): Vinflunine or Docetaxel Experimental Treatment 3 Interventions

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-PD-\[L\] 1 agent) will receive vinflunine 320 milligram per meter square (mg/m\^2) as a 20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion every 3 weeks. Treatment with either agent (choice of investigator) will be administered until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive Vinflunine or Docetaxel until the participant can commercially receive chemotherapy within the local healthcare system.

Group IV: Cohort 1 (Arm 1A): Erdafitinib Experimental Treatment 2 Interventions

Participants will be screened based on Fibroblast Growth Factor Receptor Inhibitor Clinical Trial Assay (FGFRi CTA) to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-programmed cell death protein PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 milligram (mg), once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustment are based on phosphate level and observed toxicity (adverse events \[AEs\]). Participants who enter in Long-term extension (LTE) phase will continue to receive the erdafitinib tablet as per investigator's decision.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

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 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, 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 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 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]

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 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]

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Docetaxel - StatPearls - NCBI Bookshelf - NIH Docetaxel, in combination with cisplatin, is approved by the Federal Drug Agency (FDA) as a first-line treatment for prostate cancer.

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Docetaxel - Medical Clinical Policy Bulletins The primary study endpoint was time to tumor progression (TTP), which was significantly improved with docetaxel based therapy (5.6 months) compared to standard ...