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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well erdafitinib works for people with tumors that have extra copies of the FGFR gene, which can promote cancer cell growth. Erdafitinib blocks the signals of the FGFR protein, potentially slowing or stopping tumor growth. People diagnosed with a tumor that has FGFR amplification and who have not used medications affecting calcium or phosphate levels might be suitable for this trial. Participants will take the treatment in 28-day cycles and undergo regular scans and tests to monitor progress. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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 cancer patients. In one study involving 87 patients with advanced bladder cancer, the treatment was generally well-tolerated. Most patients continued treatment despite side effects, and no treatment-related deaths occurred. Serious side effects appeared in about 38% of another group of cancer patients, but these were managed without halting treatment.

Erdafitinib has received FDA approval for treating certain cancers, indicating that its safety has been reviewed and accepted for these conditions. Overall, evidence shows that while serious side effects can occur, erdafitinib is often manageable, allowing patients to continue treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Erdafitinib is unique because it specifically targets the fibroblast growth factor receptor (FGFR), which is a new approach compared to traditional treatments like chemotherapy or radiation. Most current cancer treatments do not focus on this specific pathway, making erdafitinib a promising option for cancers driven by FGFR alterations. Researchers are excited about erdafitinib because it offers a targeted therapy that could be more effective and potentially have fewer side effects for patients whose tumors have these specific genetic changes.

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

Research has shown that erdafitinib, the treatment under study in this trial, effectively treats certain cancers, particularly those with specific gene changes. In patients with metastatic urothelial carcinoma (a type of bladder cancer), erdafitinib significantly increased survival time compared to traditional chemotherapy. Specifically, patients taking erdafitinib lived about 12.1 months on average, while those on chemotherapy lived about 7.8 months. This suggests that erdafitinib can more effectively prolong life by blocking certain abnormal signals in cancer cells. This treatment may work well for tumors with extra copies of the FGFR gene, helping to slow cancer growth. ^{3 4 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11392482/

Matching-Adjusted Indirect Comparison of the Efficacy and ... The MAIC indicates comparable efficacy of erdafitinib vs EV for overall survival and progression-free survival, with erdafitinib showing a higher probability ...

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.1088

Efficacy/safety of erdafitinib in breast cancer & FGFR alterations Six (38%) patients had serious AEs. No patients discontinued erdafitinib due to AEs. No treatment-related deaths were observed. Conclusions: ...