Erdafitinib for Solid Tumors

(RAGNAR Trial)

Recruiting at 212 trial locations

Overseen By Study Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

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

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

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: 21

Duration: Up to 4 years

316 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy of erdafitinib in terms of overall response rate (ORR) in adult and pediatric participants with advanced solid tumors with fibroblast growth factor receptor (FGFR) alterations (mutations or gene fusions). It will also evaluate ORR in pediatric participants with advanced solid tumors and FGFR alterations.

Will I have to stop taking my current medications?

The trial requires that you stop taking any chemotherapy, targeted therapy, or investigational anticancer agents at least 15 days before starting erdafitinib, or longer depending on the medication's half-life, up to a maximum of 30 days.

What data supports the effectiveness of the drug Erdafitinib for solid tumors?

Erdafitinib is a drug that has been approved for treating advanced bladder cancer, specifically urothelial carcinoma, and is being studied for other cancers like liver and lung cancer. It works by blocking certain proteins (FGFR) that help cancer cells grow. ^{1 2 3 4 5}

What safety information is available for erdafitinib (Balversa) in humans?

Erdafitinib (Balversa) has been associated with secondary maculopathy (an eye condition) in some cases. It is approved for treating certain types of bladder cancer, and its safety is being studied for other cancers as well. ^{1 2 4 6 7}

What makes the drug erdafitinib unique for treating solid tumors?

Erdafitinib is unique because it is an oral drug that specifically targets and inhibits fibroblast growth factor receptors (FGFRs), which are often altered in certain cancers. This makes it different from other treatments that may not target these specific receptors, offering a novel approach for patients with FGFR-altered tumors. ^{1 2 3 6 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults and children with advanced solid tumors that have specific genetic changes called FGFR mutations or fusions. Participants must have tried at least one treatment before, or be a child without standard therapy options. They can't join if they've had certain treatments recently, have specific resistance mutations, other active cancers needing treatment, or certain lung cancer gene changes.

Inclusion Criteria

My cancer is advanced and cannot be surgically removed, with a specific FGFR gene change.

I've had at least one treatment for my advanced cancer, or I'm a young person with a new solid tumor and no standard treatments work for me.

Measurable disease

Exclusion Criteria

I do not have any active cancer other than the one being treated.

My lung cancer has specific genetic changes.

I have a blood cancer, such as leukemia or lymphoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, or end of data collection timepoint

Up to 4 years

Every 21 days (each cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment until death, withdrawal, or end of study

6 months

Treatment Details

Interventions

• Erdafitinib

Trial Overview The study tests the drug Erdafitinib's effectiveness in shrinking tumors by measuring the overall response rate (ORR) in patients with these FGFR alterations. It includes both adult and pediatric participants who meet the criteria.

Participant Groups

Group I: Erdafitinib Experimental Treatment 1 Intervention

Participants with fibroblast growth factor receptor (FGFR) mutations and FGFR gene fusions will receive a dose of erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment, or end of data collection timepoint if there is clinical benefit in the opinion of the investigator, has been achieved.

Erdafitinib is already approved in United States, European Union for the following indications:

Approved in United States as Balversa for:

• Locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations

Approved in European Union as Balversa for:

• Locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations

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]

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 pooled analysis of 21 clinical trials involving 1468 patients with EGFR mutation-positive non-small cell lung cancer, afatinib was found to cause significantly more severe adverse events, such as rash and diarrhea, compared to erlotinib and gefitinib.

Gefitinib was associated with a higher frequency of severe hepatotoxicity compared to the other two drugs, while the overall rates of severe interstitial lung disease were low and similar across all three EGFR-TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Takeda, M., Okamoto, I., Nakagawa, K.[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]

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

Erdafitinib: First Global Approval. [2020]

3. Ireland pubmed.ncbi.nlm.nih.gov

Outcomes of patients with advanced non-small cell lung cancer treated with gefitinib (ZD1839, "Iressa") on an expanded access study. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Overview of the clinical use of erdafitinib as a treatment option for the metastatic urothelial carcinoma: where do we stand. [2022]

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

Comparison of clinical outcomes following gefitinib and erlotinib treatment in non-small-cell lung cancer patients harboring an epidermal growth factor receptor mutation in either exon 19 or 21. [2022]

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

Erdafitinib-Induced Secondary Maculopathy. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. [2022]

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]