CLINICAL TRIALS PROFILE FOR ERDAFITINIB

All Clinical Trials for Erdafitinib

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02365597 ↗	An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer	Recruiting	Janssen Research & Development, LLC	Phase 2	2015-04-22	The purpose of this study is to evaluate the objective response rate (complete response [CR]+ partial response [PR]) of the selected dose regimen in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
NCT02421185 ↗	Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493 (Erdafitinib) in Participants With Advanced Hepatocellular Carcinoma	Completed	Janssen Research & Development, LLC	Phase 1/Phase 2	2015-05-25	The purpose of this study is to determine recommended Phase 2 dose [RP2D]) and the objective response rate of JNJ-42756493 (erdafitinib) in advanced hepatocellular carcinoma (HCC) participants with fibroblast growth factor (FGF) 19 amplification.
NCT02465060 ↗	Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)	Recruiting	National Cancer Institute (NCI)	Phase 2	2015-08-12	This phase II MATCH trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.
NCT02699606 ↗	A Study to Evaluate the Clinical Efficacy of JNJ-42756493 (Erdafitinib), A Pan-Fibroblast Growth Factor Receptor (FGFR) Tyrosine Kinase Inhibitor, In Asian Participants With Advanced Non-Small-Cell Lung Cancer, Urothelial Cancer, Esophageal Cancer O	Active, not recruiting	Janssen Research & Development, LLC	Phase 2	2016-07-08	The primary purpose of this study is to evaluate objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of erdafitinib in a molecularly-defined subset of Asian participants with non-small-cell lung cancer (NSCLC), urothelial cancer, esophageal cancer and cholangiocarcinoma.
NCT02925234 ↗	The Drug Rediscovery Protocol (DRUP Trial)	Recruiting	Amgen	Phase 2	2016-08-01	This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.

Clinical Trial Conditions for Erdafitinib

Condition Name

Condition Name for Erdafitinib
Intervention	Trials
Refractory Malignant Solid Neoplasm	3
Healthy	3
Recurrent Malignant Solid Neoplasm	3
Neoplasm	3

Condition MeSH

Condition MeSH for Erdafitinib
Intervention	Trials
Urinary Bladder Neoplasms	7
Neoplasms	6
Carcinoma	6
Glioma	4

Clinical Trial Locations for Erdafitinib

Trials by Country

Trials by Country for Erdafitinib
Location	Trials
United States	261
Germany	11
Korea, Republic of	8
Belgium	7
Taiwan	7

Trials by US State

Trials by US State for Erdafitinib
Location	Trials
Texas	11
New York	10
Pennsylvania	9
North Carolina	9
Illinois	9

Clinical Trial Progress for Erdafitinib

Clinical Trial Phase

Clinical Trial Phase for Erdafitinib
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	15
Phase 1/Phase 2	2

Clinical Trial Status

Clinical Trial Status for Erdafitinib
Clinical Trial Phase	Trials
Recruiting	13
Not yet recruiting	6
Completed	3

Clinical Trial Sponsors for Erdafitinib

Sponsor Name

Sponsor Name for Erdafitinib
Sponsor	Trials
Janssen Research & Development, LLC	12
National Cancer Institute (NCI)	8
Janssen Pharmaceutical K.K.	2

Sponsor Type

Sponsor Type for Erdafitinib
Sponsor	Trials
Industry	31
NIH	8
Other	8

Erdafitinib: A Breakthrough in Treating Urothelial Carcinoma

Introduction to Erdafitinib

Erdafitinib, marketed as BALVERSA®, is a groundbreaking pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor developed by Janssen Research & Development, LLC. This drug has been making significant strides in the treatment of advanced urothelial carcinoma, particularly in patients with specific FGFR genetic alterations.

Clinical Trials Update

THOR Study: A Landmark in Erdafitinib Research

The Phase 3 THOR study (NCT03390504) has been pivotal in establishing the efficacy and safety of erdafitinib. This randomized, open-label, multicenter study compared erdafitinib with chemotherapy in patients with metastatic or unresectable urothelial carcinoma (UC) who had previously received at least one line of therapy containing a PD-1 or PD-L1 inhibitor.

• Key Findings: The study showed a 36% reduction in the risk of death with erdafitinib compared to chemotherapy. Patients receiving erdafitinib achieved a median overall survival (OS) of 12.1 months, significantly better than the 7.8 months observed in the chemotherapy arm (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.44 to 0.93; P=0.0050)[3][5].
• Progression-Free Survival (PFS) and Overall Response Rate (ORR): Erdafitinib also improved median PFS to 5.6 months versus 2.7 months for chemotherapy (HR 0.58; 95% CI, 0.41 to 0.82; P=0.0002) and achieved an ORR of 35.3% compared to 8.5% for chemotherapy[3][5].

Other Ongoing Studies

In addition to the THOR study, erdafitinib is being evaluated in several other clinical trials:

• THOR-2/BLC2003 Study: This Phase 2 study is examining erdafitinib versus investigator choice of intravesical chemotherapy in patients with high-risk non-muscle-invasive bladder cancer who have recurred after Bacillus Calmette-Guérin treatment[1].
• NORSE/BLC2002 Study: This Phase 1b/2 study is investigating erdafitinib in combination with cetrelimab in patients with locally advanced or metastatic urothelial carcinoma and FGFR3 or FGFR2 gene alterations[1].
• RAGNAR/CAN2002 Study: This Phase 2 study is evaluating the safety and efficacy of erdafitinib in patients with advanced solid tumors driven by FGFR1–4 alterations, regardless of cancer type or tumor location[1].
• TAR-210 Study: This Phase 1 study is assessing the safety and efficacy of an erdafitinib-releasing intravesical delivery system in patients with non-muscle-invasive bladder cancer and select FGFR alterations, showing early evidence of positive clinical activity and a manageable safety profile[2].

Market Analysis

Regulatory Approvals

Erdafitinib has recently received significant regulatory approvals:

• European Commission Approval: The European Commission approved erdafitinib as a once-daily oral monotherapy for the treatment of adult patients with unresectable or metastatic urothelial carcinoma, marking a significant milestone in the treatment of this patient population[3][5].
• CHMP Positive Opinion: The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for erdafitinib, paving the way for its marketing authorization in Europe[1].

Market Impact

The approval of erdafitinib is expected to significantly impact the market for urothelial carcinoma treatments:

• Unmet Need: Erdafitinib addresses a critical unmet need for targeted therapies in patients with FGFR alterations, offering a new treatment option that can improve survival and response rates compared to traditional chemotherapy[1][3].
• Competitive Landscape: With its unique mechanism of action targeting FGFR alterations, erdafitinib is poised to differentiate itself in a market dominated by immunotherapies and chemotherapies. This could lead to a shift in treatment paradigms for urothelial carcinoma[3][5].

Market Projections

Patient Population and Market Size

The market for erdafitinib is expected to grow significantly due to the prevalence of urothelial carcinoma and the specific patient population with FGFR alterations:

• Prevalence: Urothelial carcinoma is one of Europe’s most common cancers, and a subset of these patients harbor FGFR alterations, making them eligible for erdafitinib treatment[1].
• Market Size: The global bladder cancer market is projected to grow, driven by the increasing incidence of bladder cancer and the need for more effective and targeted therapies. Erdafitinib is likely to capture a significant share of this market due to its efficacy and safety profile[3].

Revenue Projections

Given the positive clinical trial results and regulatory approvals, erdafitinib is expected to generate substantial revenue:

• Sales Forecast: With its approval in key markets, erdafitinib is projected to achieve significant sales, particularly as it becomes a standard of care for patients with FGFR-altered urothelial carcinoma. The drug's unique positioning and clinical benefits are expected to drive adoption and revenue growth[3][5].

Safety and Tolerability

Adverse Events Profile

Erdafitinib has shown a manageable safety profile in clinical trials:

• Serious Adverse Events: Serious treatment-related adverse events (TRAEs) were observed in 13.3% of patients receiving erdafitinib, which is comparable to or better than chemotherapy. Grade 3 or higher adverse events occurred in 45.9% of patients on erdafitinib, and 8.1% had TRAEs that led to discontinuation of therapy[5].

Patient-Reported Outcomes

The THOR study also evaluated patient-reported outcomes, which are crucial for understanding the overall impact of erdafitinib on patients' quality of life:

• Quality of Life: While detailed patient-reported outcomes are not fully disclosed, the study's focus on these endpoints indicates a commitment to understanding the broader benefits of erdafitinib beyond just survival and response rates[3].

Expert Insights

Transforming Outcomes

Industry experts highlight the significance of erdafitinib in transforming outcomes for patients with urothelial carcinoma:

• "FGFR alterations are important oncogenic drivers in urothelial carcinoma and can be associated with adverse clinical outcomes," said Yohann Loriot, M.D., Ph.D., Institut Gustave Roussy and University of Paris-Saclay, France. "Today’s recommendation from the CHMP marks important progress towards transforming outcomes for patients diagnosed with bladder cancer with FGFR alterations."[1]

Multidisciplinary Care

The importance of a multidisciplinary care team approach is emphasized:

• "There is a critical need for a multidisciplinary care team approach, to identify patients who may benefit from erdafitinib through biomarker testing, ensuring the right treatment reaches the right patient at the right time," said Henar Hevia, Ph.D, Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine[1].

Key Takeaways

• Erdafitinib is the first targeted therapy approved for patients with unresectable or metastatic urothelial carcinoma and FGFR alterations.
• The drug has shown significant improvements in overall survival, progression-free survival, and overall response rate compared to chemotherapy.
• Erdafitinib is being evaluated in multiple clinical trials for various indications, including non-muscle-invasive bladder cancer and tumor-agnostic settings.
• The drug has a manageable safety profile and is expected to transform the treatment landscape for urothelial carcinoma.
• Market projections indicate substantial revenue growth due to its unique positioning and clinical benefits.

FAQs

What is erdafitinib and how does it work?

Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor that targets FGFR alterations in cancer cells, particularly in patients with urothelial carcinoma.

What are the key findings from the THOR study?

The THOR study showed that erdafitinib significantly improved overall survival, progression-free survival, and overall response rate compared to chemotherapy in patients with metastatic or unresectable urothelial carcinoma and FGFR alterations.

Has erdafitinib received regulatory approvals?

Yes, erdafitinib has received approval from the European Commission and a positive opinion from the CHMP for the treatment of adult patients with unresectable or metastatic urothelial carcinoma.

What is the safety profile of erdafitinib?

Erdafitinib has a manageable safety profile with serious treatment-related adverse events observed in 13.3% of patients, which is comparable to or better than chemotherapy.

What are the market projections for erdafitinib?

Erdafitinib is expected to generate significant revenue due to its unique positioning, clinical benefits, and the growing need for targeted therapies in urothelial carcinoma.

Is erdafitinib being studied in other indications?

Yes, erdafitinib is being evaluated in several other clinical trials, including studies for non-muscle-invasive bladder cancer and tumor-agnostic settings.

Sources

1. Janssen-Cilag International NV. CHMP adopts positive opinion for BALVERSA® (erdafitinib) for the treatment of adult patients. June 28, 2024.
2. Janssen. First Results with Erdafitinib-Releasing Intravesical Delivery System (TAR-210) Show Early Evidence of Positive Clinical Activity in Patients with Non-Muscle-Invasive Bladder Cancer with Select Fibroblast Growth Factor Receptor Alterations. October 22, 2023.
3. Janssen. European Commission approves BALVERSA® (erdafitinib) for adult patients with unresectable or metastatic urothelial carcinoma. August 23, 2024.
4. PubMed. Phase II Study of Erdafitinib in Patients With Tumors With FGFR Amplifications. 2023.
5. Janssen. European Commission approves BALVERSA® (erdafitinib) for adult patients with unresectable or metastatic urothelial carcinoma. August 23, 2024.