FDA Accepts sNDA for Erdafitinib in FGFR+ Advanced Urothelial Carcinoma

The FDA previously granted accelerated approval to erdafitinib as a treatment for adult patients with FGFR2/3-altered advanced or metastatic urothelial carcinoma in 2019.

Developers have submitted a supplemental new drug application (sNDA) to the FDA seeking full approval for erdafitinib (Balversa) as a treatment for patients with locally advanced or metastatic urothelial carcinoma with FGFR genetic alterations that has progressed following prior PD-L1 therapy, according to a press release from The Janssen Pharmaceutical Companies of Johnson & Johnson.¹

Supporting data for the sNDA came from the phase 3 THOR study (NCT03390504), which investigators previously presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. In a cohort of patients who received at least 1 prior line of therapy including an anti–PD-L1 agent, erdafitinib yielded a median overall survival (OS) of 12.1 months compared with 7.8 months in patients treated with investigator’s choice chemotherapy (HR, 0.64; 95% CI, 0.47-0.88; P = .005).² These interim results met the predefined threshold for erdafitinib as a superior treatment over chemotherapy, leading the independent data safety monitoring committee to recommend that investigators terminate their assessment and offer patients the chance to cross over from chemotherapy to the experimental agent.

The safety profile of erdafitinib in the THOR study was comparable with previous reports of the agent in metastatic urothelial carcinoma. Any-grade adverse effects occurred in 97.0% of patients receiving erdafitinib, which included hyperphosphatemia (78.5%), diarrhea (54.8%), and stomatitis (45.9%).

The FDA previously granted accelerated approval to erdafitinib as a treatment for adult patients with FGFR2/3-altered advanced or metastatic urothelial carcinoma in 2019.³ The accelerated approval was based on results from a phase 2 study (NCT02365597) in which erdafitinib yielded an objective response rate (ORR) of 32.2% (95% CI, 22.4%-42.0%) as determined by blinded independent central review. Developers intended to use findings from the THOR study to satisfy the FDA’s regulatory demands to validate erdafitinib’s clinical benefit in this indication.

“[Erdafitinib] continues to generate promising clinical findings for patients with FGFR-altered metastatic urothelial cancer, who often face poor disease outcomes,” Peter Lebowitz, MD, PhD, global therapeutic area head of Oncology at Janssen Research & Development, said in the press release.¹ “Through the ongoing development of this targeted therapy, we are committed to transforming bladder cancer treatment to positively impact the lives of patients.”

Investigators of the THOR study assessed erdafitinib across 2 patient cohorts, evaluating the agent vs chemotherapy among patients who received at least 1 line of therapy including an anti–PD-L1 agent in cohort 1, and comparing it with pembrolizumab (Keytruda) in patients following 1 line of therapy not containing an anti–PD-L1 agent in cohort 2. In cohort 1, patients in the experimental arm received 8 mg of erdafitinib once a day with pharmacodynamically guided uptitration to 9 mg.

The study’s primary end point was OS. Secondary end points included progression-free survival, ORR, duration of response, and safety.

References

1. Janssen submits supplemental new drug application to the U.S. Food and Drug Administration seeking full approval of BALVERSA® (erdafitinib) for the treatment of patients with locally advanced or metastatic urothelial carcinoma and selected fibroblast grow. News release. Janssen. August 28, 2023. Accessed August 29, 2023. https://shorturl.at/oqru3
2. Loriot Y, Matsubara N, Park SH, et al. Phase 3 THOR study: results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt). J Clin Oncol. 2023;41(suppl 17):LBA4619. doi:10.1200/JCO.2023.41.17_suppl.LBA4619
3. BALVERSA™ (erdafitinib) receives U.S. FDA approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma with certain FGFR genetic alterations. News release. Janssen. April 12, 2019. Accessed August 29, 2023. https://shorturl.at/dkK02