Johnson & Johnson's BALVERSA Demonstrates Survival Advantages for FGFR-Altered Urothelial Cancer

Phase 3 THOR Study

In April 2019, BALVERSA (erdafitinib), an oral FGFR kinase inhibitor, received accelerated approval from the US FDA for the treatment of adults diagnosed with locally advanced or metastatic urothelial carcinoma (mUC). This approval was specifically granted to patients who have genetic alterations in FGFR3 or FGFR2 and have experienced disease progression during or after at least one round of platinum-containing chemotherapy, which may include neoadjuvant or adjuvant platinum-containing chemotherapy within the preceding 12 months. 

Following that Janssen Pharmaceutical Companies of Johnson & Johnson presented confirmatory data from an interim analysis of Cohort 1 in the Phase III THOR study. The study assessed the efficacy of BALVERSA compared to chemotherapy in patients with metastatic or unresectable urothelial carcinoma (UC) and specific fibroblast growth factor receptor (FGFR) gene alterations. These patients had previously received treatment with an anti-programmed death ligand 1 (PD-[L]1) agent. The findings were shared during a Late-Breaking Presentation Session (Abstract #LBA4619) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The THOR study (NCT03390504) is a Phase III randomized, open-label, multicenter trial designed to evaluate the effectiveness and safety of BALVERSA. Patients were assigned to one of two cohorts based on their prior therapy: Cohort 1 consisted of patients previously treated with an anti-PD-(L)1 agent, while Cohort 2 included patients who had not received an anti-PD-(L)1 agent. Within Cohort 1, patients were randomly assigned in a 1:1 ratio to receive either BALVERSA or chemotherapy. In Cohort 2, patients were randomized to receive either BALVERSA or pembrolizumab in a 1:1 ratio. The primary endpoint of the study is overall survival (OS), while secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), patient-reported outcomes, safety, and pharmacokinetics (PK).

The interim analysis of Cohort 1 involved 266 patients, with 136 assigned to BALVERSA and 130 randomized to chemotherapy. The median follow-up duration was 15.9 months. As of the data cutoff on January 15, 2023, patients who received BALVERSA exhibited a median OS of 12.1 months, compared to 7.8 months for those who received chemotherapy. BALVERSA treatment also demonstrated a superior median PFS of 5.6 months, compared to 2.7 months with chemotherapy, along with an ORR of 45.6% versus 11.5%. These results met the predetermined criteria for superiority, leading the independent data safety monitoring committee to recommend terminating the study at the interim analysis and offering all patients randomized to chemotherapy the opportunity to switch to BALVERSA.

Consistent benefits in OS with BALVERSA over chemotherapy were observed across various subgroups, including FGFR alteration type, baseline Eastern Cooperative Oncology Group performance status, lines of prior treatment, presence of visceral metastasis, primary tumor location, and the type of chemotherapy used