Erdafitinib Induces Positive Initial Results for FGFR-Driven Malignancies


Interim analysis of the phase 2 RAGNAR trial shows promising efficacy and safety with the use of erdafitinib in patients with a variety of FGFR-driven solid tumors.

Erdafitinib (Balversa) demonstrated promising safety and efficacy in patients with a variety of FGFR-driven solid tumors, according to initial results of the phase 2 RAGNAR trial (NCT04083976).1

At the time of this planned interim analysis, responses were observed across a variety of patients with hard-to-treat advanced FGFR-positive malignancies, including glioblastoma, pancreatic cancer, and salivary gland cancers, who had used other standard treatment options before being treated with erdafitinib.

In the overall tumor-agnostic patient population, an overall response rate (ORR) assessed by independent review committee (IRC) of 29.2% (95% CI, 22.7%-36.5%) was observed, along with an investigator assessed ORR of 26.4% (95% CI, 20.1%-33.5%).2

Disease control rate (DCR) was 72.5% (95% CI, 65.3%-78.9%). Responses were observed across 14 distinct tumor types, with ORRs of 100% in salivary gland cancer (n = 5), 31% in pancreatic cancer (n = 4), and 21% in glioblastoma (n = 6).

Moreover, median duration of response (DOR) was 7.1 months (95% CI, 5.5-9.3), and at the data cutoff, 24 patients (51.1%) who had responded to treatment continued to show a response.

Additionally, median progression-free survival (PFS) was 5.2 months (95% CI, 4.0-5.6), and the median overall survival (OS) was 10.9 months (95% CI, 7.9-14.3).

The RAGNAR trial showed that the safety profile of erdafitinib was consistent with its known safety profile in metastatic urothelial carcinoma. Further, 44.9% of patients across tumor types reported grade 3 or higher adverse events (AEs), which were manageable with supportive care and treatment interruptions or reductions, when necessary. Drug-related AEs led to a discontinuation rate of 7.3%.

"Diagnostic advances in the identification of FGFR gene alterations have opened the door to targeted, tumor-agnostic treatment approaches for patients," said principal study investigator Yohann Loriot, MD, PhD, Institut Gustave Roussy and University of Paris-Saclay, in the press release.1 "Results from the RAGNAR study show that, through the targeted inhibition of FGFR receptors, we may be able to tailor treatment for patients with advanced FGFR-driven cancers, regardless of tumor location or histology."

The interventional, phase 2 RAGNAR study looks to evaluate the efficacy and safety of erdafitinib in patients with advanced or metastatic solid tumors and FGFR gene alterations, regardless of tumor location or histology.

In the interim analysis, 178 patients with 32 distinct solid tumor histologies were included, each identified by local molecular testing or central next-generation sequencing (NGS). The most common tumor types were cholangiocarcinoma (n = 31), high-grade glioma (n = 29), breast cancer (n = 14), pancreatic cancer (n = 13) and squamous non-small cell lung cancer (n = 11). Additionally, patients with salivary gland, parathyroid carcinomas, and tumors of unknown primary origin were included.

Enrollment in the trial is open to patients who have a histologic demonstration of an unresectable, locally advanced, or metastatic solid tumor malignancy with a FGFR mutation or FGFR gene fusion, measurable disease, and documented progression of disease. Further, study participants were heavily pretreated, with 74.7% (n = 133) of patients having received 2 or more prior lines of therapy.3

The primary end point of the study is ORR as assessed by an IRC, with secondary end points including DOR, DCR, clinical benefit rate, PFS, OS, plasma concentrations of erdafitinib, adverse events, and changes in health-related quality of life.

"Janssen is committed to advancing precision medicine approaches for the treatment of patients with biomarker-driven cancers, an area of clear unmet need," stated Kiran Patel, MD, vice president, clinical development, solid tumors of Janssen Research & Development, LLC, in the press release. "RAGNAR, Janssen's first tumor-agnostic study, demonstrates our commitment to understand the biology of disease, identify new treatment pathways and improve patient outcomes. We look forward to progressing the development of Balversa for these patients and sharing additional updates on this program in the future."

The primary analysis for all patients treated in the RAGNAR trial is expected to be released later this year.

  1. Janssen presents initial results from the phase 2 RAGNAR study of balversa® (erdafitinib) in patients with advanced solid tumors with FGFR alterations. The Janssen Pharmaceutical Companies of Johnson & Johnson news release. Published: June 07, 2022. Accessed: June 13, 2022.
  2. Loriot Y, Schuler MH, Iyer G, et al. Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: Interim analysis (IA) results. J Clin Oncol. 2022;40:16(abstr 3007). doi:10.1200/JCO.2022.40.16_suppl.3007
  3. A study of erdafitinib in participants with advanced solid tumors and fibroblast growth factor receptor (FGFR) gene alterations. Updated: May 20, 2022. Accessed June 13, 2022.
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