Erdafitinib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Calcium supplements, Phosphate laxatives

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: Unknown

Duration: Up to 3 years

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that can increase serum calcium or phosphate levels, as well as strong inhibitors or inducers of certain enzymes (CYP3A4 and CYP2C9) at least 2 weeks before starting the study treatment. If you are on these medications, you will need to stop them before participating.

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

Erdafitinib is approved for treating advanced bladder cancer and is being studied for other cancers like liver and lung cancer, showing promise due to its ability to target specific cancer cell growth pathways. ^{1 2 3 4 5}

Is erdafitinib safe for humans?

Erdafitinib, also known as Balversa, is generally considered safe for humans, but it can cause side effects like secondary maculopathy (an eye condition). It is important to discuss potential risks with a healthcare provider. ^{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 JNJ-42756493 (erdafitinib) works in treating patients with tumors that have more copies of the FGFR gene than is normal (amplification). 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.

Research Team

Alain C Mita

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with various cancers, like multiple myeloma and lymphoma, who have tumors with an abnormal increase in FGFR gene copies. Participants should be suitable for biopsies, CT scans, MRI scans, and biospecimen collection.

Inclusion Criteria

I am not taking medications that increase my calcium or phosphorus levels.

I am not allergic to erdafitinib or similar drugs.

Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol

Exclusion Criteria

I am not taking medications that increase my calcium levels, including supplements.

I do not have bladder or urothelial tract cancer.

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

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. Patients also undergo CT and MRI throughout the study.

Up to 3 years

Follow-up

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

3 years

Treatment Details

Interventions

• Erdafitinib

Trial Overview The study is testing Erdafitinib's effectiveness on patients whose cancer involves FGFR amplifications. It's a phase II trial where Erdafitinib is given to see if it can stop the cancer cells from multiplying by blocking the action of an abnormal protein.

Participant Groups

Group I: Treatment (erdafitinib) 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. Patients also undergo CT and MRI throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial.

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]