Erdafitinib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Calcium supplements, Vitamin D, others

Disqualifiers: Corneal disorder, Hyperphosphatemia, Renal impairment, Cardiovascular disease, 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: 31

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called erdafitinib for individuals with tumors that have specific genetic changes known as FGFR mutations or fusions. Erdafitinib blocks signals that prompt cancer cells to grow, potentially stopping or killing these cells. Suitable candidates for this trial have cancers with FGFR mutations or fusions, excluding bladder cancer. Participants will take the medication daily and undergo regular check-ups, including blood tests and scans. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant cancer research.

Will I have to stop taking my current medications?

The trial requires that you avoid medications that increase calcium or phosphate levels, such as certain supplements and laxatives. You also cannot take strong inhibitors or inducers of CYP3A within 2 weeks before starting the trial. If you are on these medications, you may need to stop or switch them before participating.

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

Research has shown that erdafitinib has been tested for safety in people with cancer. In earlier studies, most participants tolerated it well. However, like any treatment, some experienced side effects. Specifically, about 16.9% of patients had side effects related to genetic changes, and 9.8% had side effects linked to a specific gene fusion.

The FDA has already approved erdafitinib for other uses, indicating it has passed safety checks for those conditions. However, individual reactions can vary, and side effects may differ. It is important to consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Erdafitinib is unique because it specifically targets cancers with FGFR mutations or fusions, which are not typically addressed by standard treatments like chemotherapy or immunotherapy. This drug works by inhibiting the fibroblast growth factor receptor (FGFR), a mechanism that is different from the traditional approaches. Researchers are excited because this targeted approach could provide more effective treatment options for patients whose cancers have these specific genetic alterations, potentially leading to better outcomes and fewer side effects compared to conventional treatments.

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

Research has shown that erdafitinib can help treat tumors with specific genetic changes called FGFR mutations or fusions. In this trial, participants will receive erdafitinib as part of the study's treatment arm. Studies have found that about 25% of patients, or one in four, experienced a positive effect from the treatment. Patients with advanced or spreading tumors lived longer when taking erdafitinib compared to those receiving standard chemotherapy. It has also proven effective for breast cancer patients who have tried other treatments without success. Erdafitinib blocks a protein that signals cancer cells to grow, helping to stop or kill them. Overall, erdafitinib appears promising for treating these specific types of cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Alain C Mita

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients with tumors that have specific genetic changes called FGFR mutations or fusions. Participants should be willing to undergo imaging tests like MRI and CT scans, provide tissue samples, and have not responded to standard treatments.

Inclusion Criteria

Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

Patients must fulfill all eligibility criteria outlined in the MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)

My phosphate levels are not higher than normal despite treatment.

Exclusion Criteria

I do not have any non-healing wounds or ulcers.

I have never had high phosphate levels in my blood.

I do not have any current eye disorders affecting my cornea or retina.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive erdafitinib orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Visits every 28 days for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for 2 years and then every 6 months for 1 year.

3 years

Follow-up visits every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Erdafitinib

Trial Overview The focus of this phase II trial is on Erdafitinib (JNJ-42756493), a kinase inhibitor medication. It's designed to block abnormal proteins from signaling cancer cells to grow, potentially stopping their spread and killing them.

How Is the Trial Designed?

Group I: Subprotocol K2 (FGFR mutation or fusion) Experimental Treatment 5 Interventions

Patients receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI, and tumor biopsy throughout the study. (CLOSED TO ACCRUAL 02/25/2022)

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]

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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308849

Erdafitinib or Chemotherapy in Advanced or Metastatic ... Erdafitinib therapy resulted in significantly longer median overall survival than chemotherapy among patients with advanced or metastatic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11224843/

Tumour-agnostic efficacy and safety of erdafitinib in patients ... Efficacy was observed across patients with FGFR1–3 mutations and fusions (appendix p 23). The overall response rate was 25% (95% CI 16–37) in the prespecified ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11623915/

Phase 2 Study of Erdafitinib in Patients with Tumors with ... This study met its primary endpoint in patients with several pretreated solid tumor types harboring FGFR1–3 mutations or fusions. These findings ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1088

Efficacy and safety of erdafitinib in adults with breast ... Erdafitinib demonstrated clinically meaningful activity in heavily pretreated patients with breast cancer and prespecified FGFR alterations.

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.907377/full

Safety and efficacy of the pan-FGFR inhibitor erdafitinib in ... Conclusion: Erdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With ...

6. balversahcp.com balversahcp.com/clinical-information/mechanism-of-action

Mechanism of Action - BALVERSA™ (erdafitinib) HCP BALVERSA® demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer. 1. BALVERSA® ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9909824/

Safety and efficacy of the pan-FGFR inhibitor erdafitinib in ... In efficacy analysis, erdafitinib can increase the PFS significantly, among which, patients with FGFR mutations have a better response than those with fusions, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/212018Orig1s000MultidisciplineR.pdf

212018Orig1s000 - accessdata.fda.gov All patients must have had FGFR mutation or fusion: a. FGFR3 gene ... The erdafitinib clinical safety database contains pooled data ...

9. nature.com nature.com/articles/s41598-025-11411-1

Data mining and safety analysis of FGFR tyrosine kinase ... Our study provides an in-depth analysis of the post-market safety profiles for FGFR-TKIs, specifically erdafitinib, pemigatinib, and futibatinib ...