Erdafitinib Combo for Bladder Cancer

Recruiting at 152 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

125 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Erdafitinib Combo for Bladder Cancer?

Erdafitinib has been approved for treating advanced bladder cancer with specific genetic changes (FGFR3 or FGFR2 alterations) and has shown antitumor activity in studies. It is also being explored for other cancers, indicating its potential effectiveness. ^{1 2 3 4 5}

Is the Erdafitinib Combo for Bladder Cancer safe for humans?

Erdafitinib has been shown to be generally tolerable in patients with advanced urothelial carcinoma, but it can cause side effects like secondary maculopathy (an eye condition). Safety data from studies on erdafitinib in other cancers also suggest it is generally safe, but side effects can occur. ^{1 2 3 6 7}

What makes the drug erdafitinib unique for treating bladder cancer?

Erdafitinib is unique because it is the first oral drug approved to target specific genetic changes (FGFR3/2 alterations) in bladder cancer, offering a new option for patients who have not responded to other treatments like chemotherapy. ^{1 3 4 8 9}

What is the purpose of this trial?

The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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.

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

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

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

Treatment Details

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.

Participant Groups

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+

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

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]

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 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]

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 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 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]

References

1. Germany 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. [2022]

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

Erdafitinib-Induced Secondary Maculopathy. [2023]

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

Erdafitinib: First Global Approval. [2020]

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

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

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

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

6. England 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the pan-FGFR inhibitor erdafitinib in advanced urothelial carcinoma and other solid tumors: A systematic review and meta-analysis. [2023]

8. 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]

9. Spain pubmed.ncbi.nlm.nih.gov

Erdafitinib to treat urothelial carcinoma. [2019]