Erdafitinib for Bladder Cancer

(THOR Trial)

Recruiting at 413 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

629 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-\[L\]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).

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.

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

Erdafitinib is an oral drug approved for treating advanced bladder cancer in patients with specific genetic changes (FGFR3/2 alterations) who have not responded to certain chemotherapies. It has shown antitumor activity in studies and is the first oral treatment option for this condition. ^{1 2 3 4 5}

What safety data exists for Erdafitinib in humans?

Erdafitinib is generally considered safe for humans, but common side effects include hyperphosphatemia (high phosphate levels in the blood) and retinopathy (eye damage), which require regular monitoring. ^{1 2 5 6 7}

What makes the drug erdafitinib unique for treating bladder cancer?

Erdafitinib is unique because it is the first oral drug specifically targeting FGFR (fibroblast growth factor receptor) alterations in bladder cancer, offering a new option for patients who have progressed after platinum-based chemotherapy. ^{1 2 5 8 9}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

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

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]

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]

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, 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]

References

1. 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]

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

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. [2023]

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

Schedule dependent efficacy of gefitinib and docetaxel for bladder cancer. [2018]

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

Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

Erdafitinib to treat urothelial carcinoma. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Evidence and Selecting Patients for Treatment with Erdafitinib in Advanced Urothelial Carcinoma. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Erdafitinib: First Global Approval. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Management of Fibroblast Growth Factor Inhibitor Treatment-emergent Adverse Events of Interest in Patients with Locally Advanced or Metastatic Urothelial Carcinoma. [2023]

9. 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]