Erdafitinib for Solid Tumors

(RAGNAR Trial)

Not currently recruiting at 249 trial locations

Overseen By Study Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Chemotherapy, Targeted therapy

Disqualifiers: Urothelial carcinoma, Hematologic malignancy, 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: 21

Duration: Up to 4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests erdafitinib (Balversa) as a new treatment for individuals with certain advanced solid tumors. Researchers aim to evaluate its effectiveness for tumors with specific changes in the fibroblast growth factor receptor (FGFR) gene. The trial seeks participants who have tried at least one other unsuccessful treatment for their advanced cancer or children with newly diagnosed tumors lacking other treatment options. The study aims to determine if erdafitinib can shrink these hard-to-treat tumors. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to potentially benefit from an innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any chemotherapy, targeted therapy, or investigational anticancer agents at least 15 days before starting erdafitinib, or longer depending on the medication's half-life, up to a maximum of 30 days.

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 various solid tumors, particularly those with FGFR gene changes. One study found a 21% success rate in shrinking tumors in patients with these genetic changes, indicating that the treatment can be effective against certain tumors.

Regarding safety, erdafitinib has been used in other studies and is generally well-tolerated. In one study, side effects were considered acceptable and usually manageable. The FDA has approved erdafitinib for treating a type of bladder cancer, suggesting it is safe for humans, although safety can vary depending on the condition and the individual.

Prospective trial participants should discuss potential side effects and risks with their healthcare provider. This discussion can help clarify how the treatment might affect them personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Erdafitinib is unique because it directly targets fibroblast growth factor receptors (FGFR), which are often altered in certain solid tumors. Unlike standard chemotherapy and radiation that attack cancer cells more generally, erdafitinib zeroes in on these specific genetic mutations and gene fusions, potentially leading to more personalized and effective treatment. Researchers are excited about erdafitinib because its targeted approach could result in fewer side effects and better outcomes for patients with FGFR mutations, offering new hope where existing treatments may fall short.

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

Research has shown that erdafitinib may help treat certain solid tumors with changes in the FGFR gene. One study found that patients with tumors featuring FGFR1–3 mutations or fusions, who had already received other treatments, responded well to erdafitinib. In patients with advanced bladder cancer, erdafitinib extended survival compared to chemotherapy. This suggests erdafitinib might be effective for tumors with specific FGFR changes. However, another study did not meet its main goals for hard-to-treat tumors, indicating mixed results. The drug appears most effective for certain cancers related to FGFR changes. Participants in this trial will receive erdafitinib to evaluate its effectiveness in treating solid tumors with FGFR mutations and gene fusions. ^{1 3 4 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults and children with advanced solid tumors that have specific genetic changes called FGFR mutations or fusions. Participants must have tried at least one treatment before, or be a child without standard therapy options. They can't join if they've had certain treatments recently, have specific resistance mutations, other active cancers needing treatment, or certain lung cancer gene changes.

Inclusion Criteria

My cancer is advanced and cannot be surgically removed, with a specific FGFR gene change.

I've had at least one treatment for my advanced cancer, or I'm a young person with a new solid tumor and no standard treatments work for me.

Measurable disease

Exclusion Criteria

I do not have any active cancer other than the one being treated.

My lung cancer has specific genetic changes.

I have a blood cancer, such as leukemia or lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, or end of data collection timepoint

Up to 4 years

Every 21 days (each cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment until death, withdrawal, or end of study

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Erdafitinib

Trial Overview The study tests the drug Erdafitinib's effectiveness in shrinking tumors by measuring the overall response rate (ORR) in patients with these FGFR alterations. It includes both adult and pediatric participants who meet the criteria.

How Is the Trial Designed?

Group I: Erdafitinib Experimental Treatment 1 Intervention

Participants with fibroblast growth factor receptor (FGFR) mutations and FGFR gene fusions will receive a dose of erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment, or end of data collection timepoint if there is clinical benefit in the opinion of the investigator, has been achieved.

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?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

In a pooled analysis of 21 clinical trials involving 1468 patients with EGFR mutation-positive non-small cell lung cancer, afatinib was found to cause significantly more severe adverse events, such as rash and diarrhea, compared to erlotinib and gefitinib.

Gefitinib was associated with a higher frequency of severe hepatotoxicity compared to the other two drugs, while the overall rates of severe interstitial lung disease were low and similar across all three EGFR-TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Takeda, M., Okamoto, I., Nakagawa, K.[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]

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]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04083976

NCT04083976 | A Study of Erdafitinib in Participants With ... The purpose of this study is to evaluate the efficacy of erdafitinib in terms of overall response rate (ORR) in adult and pediatric participants with ...

3. 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 ...

4. jnj.com jnj.com/innovativemedicine/emea/newsroom/oncology/chmp-adopts-positive-opinion-for-balversa-erdafitinib-for-the-treatment-of-adult-patients-with-unresectable-or-metastatic-urothelial-carcinoma-with-susceptible-fgfr3-genetic-alterations

CHMP adopts positive opinion for BALVERSA® (erdafitinib ... The CHMP's recommendation is based on results from Cohort 1 of the Phase 3 THOR study, which showed a 36 percent reduction in the risk of death with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11623914/

Phase 2 Study of Erdafitinib in Patients with Tumors with ... Erdafitinib did not meet its primary endpoint of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1–4 ...

6. jnjmedicalconnect.com jnjmedicalconnect.com/products/balversa/medical-content/use-of-balversa-in-non-small-cell-lung-cancer

Use of BALVERSA in Non-Small Cell Lung Cancer An ongoing, phase 2, open-label, single-arm, global, multicenter study evaluating the efficacy and safety of BALVERSA in adult and pediatric patients.

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

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