Erdafitinib for Cancer

Recruiting at 124 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 agents, CYP2C9 agents

Disqualifiers: Pregnancy, Uncontrolled infection, Cardiovascular diseases, others

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: Unknown

Duration: Up to 2 years

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II Pediatric MATCH trial studies how well erdafitinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with FGFR mutations that have spread to other places in the body and have come back or do not respond to treatment. Erdafitinib may stop the growth of cancer cells with FGFR mutations by blocking some of the enzymes needed for cell growth.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. You cannot be on other anti-cancer agents, investigational drugs, or certain medications that affect specific liver enzymes (CYP3A4 and CYP2C9). If you're on corticosteroids, you need to be on a stable or decreasing dose for at least 7 days before joining the trial.

Is erdafitinib safe for humans?

Erdafitinib, also known as Balversa, is generally considered safe for treating certain cancers, but it can cause side effects like secondary maculopathy (eye condition) and has been associated with other adverse effects. It's important to discuss potential risks with your doctor. ^{1 2 3 4 5}

What makes the drug erdafitinib unique for treating cancer?

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 like urothelial carcinoma. This makes it particularly effective for patients with FGFR alterations who have not responded well to other treatments like chemotherapy. ^{1 2 3 6 7}

What data supports the effectiveness of the drug Erdafitinib (Balversa) for cancer treatment?

Erdafitinib is approved for treating advanced urothelial carcinoma, a type of bladder cancer, 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 5 8}

Who Is on the Research Team?

Alice Lee

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 12 months to 21 years with advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have FGFR mutations. Participants must be able to swallow tablets, have not been treated with erdafitinib before, and meet specific health criteria like normal bilirubin levels and kidney function.

Inclusion Criteria

I have never taken erdafitinib or similar FGFR inhibitor drugs.

My bilirubin levels are within the normal range for my age.

Your heart's QTc interval is less than or equal to 480 milliseconds.

Exclusion Criteria

Investigational drugs: patients who are currently receiving another investigational drug are not eligible

I am not pregnant or breastfeeding, and if capable of having children, I agree to use birth control during and for 3 months after the study.

I have a history of serious heart rhythm problems or specific heart muscle conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Includes imaging and biopsy

Treatment

Participants receive erdafitinib orally once daily on days 1-28 of each cycle, repeating every 28 days for up to 26 cycles

Up to 2 years

Regular imaging and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

Periodic follow-up visits

Exploratory Genomic Profiling

Evaluation of changes in tumor genomics over time through circulating tumor DNA

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Erdafitinib

Trial Overview The study tests the effectiveness of erdafitinib in patients whose cancer has returned or is resistant to treatment. It aims to see if this drug can stop cancer growth by blocking enzymes needed for cell growth. The trial includes imaging tests like X-rays and MRIs as well as biospecimen collection.

How Is the Trial Designed?

Group I: Treatment (erdafitinib) Experimental Treatment 11 Interventions

Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

Citations

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. 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]

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

Erdafitinib: First Global Approval. [2020]

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. Ireland pubmed.ncbi.nlm.nih.gov

Fatal interstitial lung disease associated with high erlotinib and metabolite levels. A case report and a review of the literature. [2022]

7. 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]

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]