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

35 Participants Needed

Trial Summary

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.

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

Erdafitinib (Balversa) is approved for treating advanced bladder cancer with specific genetic changes and is being studied for other cancers like liver and lung cancer. It works by blocking certain proteins that help cancer cells grow. ^{1 2 3 4 5}

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 in some cases. ^{1 2 3 5 6}

How is the drug erdafitinib unique in 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 7 8}

What is the purpose of this trial?

This phase II MATCH treatment trial tests how well erdafitinib (JNJ-42756493) works in treating patients with tumors that have FGFR mutations or fusions. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them.

Research Team

Alain C Mita

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

Erdafitinib-Induced Secondary Maculopathy. [2023]

4. 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]

5. 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]

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]