FDA Approval Sought for Erdafitinib in Locally Advanced or Metastatic FGFR3+ Urothelial Carcinoma

A supplemental new drug application (sNDA) seeking the full approval of erdafitinib (Balversa) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma harboring susceptible FGFR3 alterations who progressed during or following at least 1 line of a PD-1/PD-L1 inhibitor in the locally advanced or metastatic setting or within 12 months of neoadjuvant or adjuvant therapy, has been submitted to the FDA.¹

The sNDA is supported by data from cohort 1 of the phase 3 THOR trial (NCT03390504), which demonstrated that treatment with erdafitinib led to a 36% reduction in the risk of death compared with chemotherapy (HR, 0.64; 95% CI, 0.47-0.88; P = .005).² At a median follow-up of 15.9 months, patients treated with erdafitinib (n = 136) experienced a median overall survival (OS) of 12.1 months compared with 7.8 months for those given chemotherapy (n = 130).

“[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, stated in a news release. “Through the ongoing development of this targeted therapy, we are committed to transforming bladder cancer treatment to positively impact the lives of patients.”

In April 2019, the FDA granted accelerated approval to erdafitinib for the treatment of adult patients with locally advanced or metastatic bladder cancer with an FGFR3 or FGFR2 alteration that has progressed on platinum-containing chemotherapy.³

THOR was a randomized, controlled, open-label, multicenter trial designed as a confirmatory study for erdafitinib.¹ Cohort 1 included patients at least 18 years of age with metastatic or unresectable urothelial carcinoma who had confirmed disease progression.² One to 2 lines of prior systemic therapy, including prior treatment with an anti–PD-1 or –PD-L1 therapy, were required. Patients also needed to have an ECOG performance status of 0 to 2 and an FGFR2/3 mutation or fusion.

Patients were randomly assigned 1:1 to received 8 mg of oral erdafitinib once per day with pharmacodynamically guided up-titration to 9 mg, or physician’s choice of chemotherapy consisting of docetaxel or vinflunine once every 3 weeks. Patients were stratified by region (North America vs European Union vs rest of world), disease distribution (presence vs absence of visceral metastases), and ECOG performance status (0 or 1 vs 2).

OS served as the trial’s primary end point. Key secondary end points included progression-free survival (PFS), overall response rate (ORR), and safety.

Additional data showed erdafitinib generated an OS benefit vs chemotherapy across key subgroups.

The median PFS was 5.6 months for patients treated with erdafitinib compared with 2.7 months for those given chemotherapy (HR, 0.58; 95% CI, 0.44-0.78; P = .0002). Erdafitinib elicited an ORR of 45.6%, including complete response (CR) and partial response (PR) rates of 6.6% and 39.0%, respectively. The ORR for chemotherapy was 11.5% with a CR rate of 0.8% and a PR rate of 10.8% (relative risk, 3.94; 95% CI, 2.37-6.57; P < .001).

Regarding safety, 13.3% of patients treated with erdafitinib who experienced adverse effects (AEs; n = 135) experienced serious treatment-related AEs (TRAEs) compared with 24.1% of evaluable patients given chemotherapy (n = 112). One treatment-related death occurred in the erdafitinib arm compared with 6 in the chemotherapy arm.

Any-grade TRAEs occurred in 97.0% of patients in the erdafitinib arm vs 86.6% of patients in the chemotherapy arm. The rates of grade 3/4 TRAEs were 45.9% and 46.4%, respectively. The most common TRAEs in the erdafitinib arm consisted of hyperphosphatemia (any grade, 78.5%; grade 3/4, 5.2%), diarrhea (54.8%; 3.0%), stomatitis (45.9%, 8.1%), dry mouth (38.5%; 0%), palmar-plantar erythrodysesthesia syndrome (30.4%; 9.6%), and onycholysis (23.0%; 5.9%).

The most common TRAEs in the chemotherapy arm included anemia (any grade, 27.7%; grade 3/4, 6.3%), alopecia (21.4%; 0%), nausea (19.6%; 1.8%), neutropenia (18.8%; 13.4%), leukopenia (11.6%; 8.0%), and febrile neutropenia (8.0%; 8.9%).

TRAEs led to treatment discontinuation in 8.1% of patients in the erdafitinib arm vs 13.4% in the chemotherapy arm.

Any-grade AEs of interest included nail disorders (66.7% for erdafitinib vs 5.4% for chemotherapy), skin disorders (54.8% vs 12.5%), central serous retinopathy (17.0% vs 0%), and other eye disorders (42.2% vs 5.4%).

Results from cohort 2 of THOR will be presented at an upcoming medical meeting.¹

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://www.janssen.com/janssen-submits-supplemental-new-drug-application-us-food-and-drug-administration-seeking-full
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. FDA grants accelerated approval to erdafitinib for metastatic urothelial carcinoma. News release. FDA. April 12, 2019. Accessed August 29, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-erdafitinib-metastatic-urothelial-carcinoma