Erdafitinib for Cancer

Not currently recruiting at 132 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests erdafitinib (Balversa), a treatment that might stop the growth of cancer cells with specific FGFR mutations. It targets patients with hard-to-treat cancers, such as certain solid tumors and lymphomas, that have spread or returned after other treatments. The trial aims to assess erdafitinib's effectiveness in these cases. Individuals with solid tumors featuring FGFR mutations who have not responded to other treatments might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that erdafitinib is likely to be safe for humans?

Research has shown that erdafitinib has been tested in patients with other types of cancer, such as bladder cancer. In these studies, hundreds of patients received the treatment, and results indicated that erdafitinib was generally well-tolerated. Most patients experienced side effects similar to those from other cancer treatments.

The most common side effects included changes in vision and dry mouth, while some patients experienced skin or nail issues. In rare cases, more serious side effects occurred.

Erdafitinib is already approved by the FDA for treating certain cancers with FGFR mutations, indicating it is safe enough for use in these conditions. However, individual experiences can vary, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Erdafitinib is unique because it targets specific genetic changes in cancer cells, called FGFR mutations, which are not addressed by most standard treatments like chemotherapy or immunotherapy. This targeted approach could potentially offer more effective results for those with these mutations. Additionally, erdafitinib is taken orally, which may provide a more convenient option compared to treatments that require hospital visits for infusions. Researchers are excited because this precision medicine can lead to better outcomes with potentially fewer side effects for patients with certain types of cancer.

What evidence suggests that erdafitinib might be an effective treatment for cancer?

Research shows that erdafitinib effectively treats cancers with FGFR mutations. Studies have found that erdafitinib can reduce the risk of death by 36% compared to chemotherapy for patients with certain cancers. Specifically, patients with metastatic urothelial carcinoma, a type of bladder cancer, lived longer on average—12.1 months compared to 7.8 months for those receiving chemotherapy. These results suggest that erdafitinib may slow the growth of cancer cells with FGFR mutations by blocking the enzymes they need to grow. While these findings are encouraging, they are based on studies of other cancers, so erdafitinib is still being tested for the specific conditions in this trial. Participants in this trial will receive erdafitinib as part of the study treatment. ^{3 6 7 8 9}

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]

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]

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]

Citations

1.

balversahcp.com

balversahcp.com/clinical-information/efficacy

Efficacy | BALVERSA® (erdafitinib) HCP

BALVERSA® significantly reduced the risk of death by 36% vs chemotherapy. The efficacy of BALVERSA® was studied in a phase 3, randomized, open-label, ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2308849

Erdafitinib or Chemotherapy in Advanced or Metastatic ...

Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR ...

3.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-erdafitinib-locally-advanced-or-metastatic-urothelial-carcinoma

FDA approves erdafitinib for urothelial carcinoma

Median OS was 12.1 months (95% CI: 10.3, 16.4) for patients who received erdafitinib and 7.8 months (95% CI: 6.5, 11.1) for those who received ...

4.

jnj.com

jnj.com/media-center/press-releases/european-commission-approves-balversa-erdafitinib-for-adult-patients-with-unresectable-or-metastatic-urothelial-carcinoma

European Commission approves BALVERSA ...

The results demonstrate median overall survival (OS) of over one year was achieved in patients receiving erdafitinib at the data cut-off, ...

5.

urotoday.com

urotoday.com/conference-highlights/aua-2024/aua-2024-bladder-cancer/151853-aua-2024-first-safety-and-efficacy-results-of-the-tar-210-erdafitinib-intravesical-delivery-system-in-patients-with-non-muscle-invasive-bladder-cancer-with-select-fgfr-alterations.html

First Safety and Efficacy Results of the TAR-210 Erdafitinib ...

Dr. Antoni Vilaseca presented presented the first safety and efficacy results of the TAR-210 erdafitinib intravesical delivery system in ...

6.

balversahcp.com

balversahcp.com/clinical-information/safety

Safety | BALVERSA® (erdafitinib) HCP

The safety population described in the Warnings and Precautions reflect a pooled safety population of 479 patients with advanced urothelial cancer and FGFR ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf

BALVERSA (erdafitinib) tablets, for oral use - accessdata.fda.gov

The safety of BALVERSA was evaluated in the BLC2001 study that included 87 patients with locally advanced or metastatic urothelial carcinoma which had ...

8.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8515

Efficacy and safety of erdafitinib in adults with NSCLC ...

Safety data were consistent with erdafitinib safety profile. Clinical trial information: NCT04083976. This is an ASCO Meeting Abstract from ...

9.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/n/ht8269678067037582/

Erdafitinib (Balversa) - NCBI Bookshelf - NIH

Other AEs and the overall safety profile were comparable between erdafitinib and chemotherapy. ... erdafitinib to other patients with bladder cancer.