Balversa improved overall survival versus chemotherapy in patients with metastatic or unresectable urothelial carcinoma and selected fibroblast growth factor receptor gene alterations after prior anti-PD-(L)1 treatment
The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from an interim analysis of Cohort 1 of the Phase III THOR study, evaluating treatment with Balversa (erdafitinib) versus chemotherapy in patients with metastatic or unresectable urothelial carcinoma (UC) and selected fibroblast growth factor receptor (FGFR) gene alterations who had received prior treatment with an anti-programmed death ligand 1 (PD-[L]1) agent
In this cohort, the study met its primary endpoint of overall survival (OS) and reduced the risk of death by 36 percent. Following the accelerated approval of Balversa in 2019, these confirmatory data were featured in a Late-Breaking Presentation Session (Abstract # LBA4619) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
“These results represent the first data from a randomized, controlled trial evaluating Balversa for the treatment of patients with FGFR-altered urothelial carcinoma, who often experience poor disease outcomes,” said Yohann Loriot* M.D., Ph.D., Institut Gustave Roussy and University of Paris-Saclay, France, and principal study investigator. “The use of Balversa in this setting supports recommendations for FGFR testing in all patients with metastatic urothelial cancer.”
THOR (NCT03390504) is a Phase III randomized, open-label, multicenter study evaluating the efficacy and safety of Balversa. Patients were categorized to one of two cohorts based on the type of prior therapy they had received: prior treatment with an anti-PD-(L)1 agent (Cohort 1) or prior treatment not containing an anti-PD-(L)1 agent (Cohort 2). Patients in Cohort 1 were randomized to receive either Balersa or chemotherapy in a 1:1 ratio and patients in Cohort 2 were randomized to receive either Balversa or pembrolizumab in a 1:1 ratio. The primary endpoint of the study is OS; progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), patient-reported outcomes, safety and pharmacokinetics (PK) are secondary endpoints.
Results from the interim analysis of Cohort 1 included data inclusive of 266 patients where 136 patients were assigned to Balversa and 130 were randomized to chemotherapy. Median follow-up was 15.9 months. At the data cutoff on January 15, 2023, OS in patients who received Balversa was 12.1 months compared to 7.8 months in patients who received chemotherapy (Hazard Ratio (HR) 0.64; [95 percent Confidence Interval (CI), 0.47-0.88]; p=0.0050). Treatment with Balversa also showed an improvement in median PFS compared to chemotherapy of 5.6 months versus 2.7 months (HR 0.58; [95 percent CI, 0.44-0.78]; p=0.0002) and an ORR of 45.6 percent versus 11.5 percent (Relative Risk (RR) 3.94; [95 percent CI, 2.37-6.57]; p<0.001). these data met the predefined criteria for superiority, and the independent data safety monitoring committee recommended that the study be stopped at the interim analysis and that all patients randomized to chemotherapy be offered the opportunity to cross-over to balversa.
Across all subgroups, OS benefit with Balversa versus chemotherapy was consistently observed. Subgroups included FGFR alteration type, baseline Eastern Cooperative Oncology Group performance status, lines of prior treatment, visceral metastasis, primary tumor location and type of chemotherapy.
The safety profile of Balversa observed in THOR was consistent with the known safety profile of Balversa in metastatic urothelial carcinoma (mUC). Serious treatment-related adverse events (TRAEs) were observed in 13.3 percent of patients who received Balversa and 24.1 percent of patients randomized to chemotherapy, and grade three or higher adverse events were observed in 45.9 percent of patients on Balversa and 46.4 percent on chemotherapy. 8.1 percent of patients who received Balversa and 13.4 percent of patients who received chemotherapy had TRAEs that lead to discontinuation of therapy. Central serous retinopathy occurred in 17 percent of patients who received Balversa. TRAEs leading to death were reported in one patient who received Balversa and six patients who received chemotherapy.
Final Results from Phase II NORSE Study Evaluating Balversa and Cetrelimab Combination Therapy; Also presented were data from the Phase II NORSE study evaluating Balversa alone and in combination with cetrelimab, an investigational anti-programmed death receptor-1 (PD-1) monoclonal antibody, as first-line treatment of patients with mUC who were ineligible for cisplatin-based chemotherapy and who had FGFR alterations. Both the combination and monotherapy treatment demonstrated a clinically meaningful response, with an ORR of 54.5 percent (95 percent CI, 38.8-69.6) in the combination arm and 44.2 percent (95 percent CI, 29.1-60.1) in the monotherapy arm, and was well-tolerated in patients. In the combination arm, six patients achieved a complete response and one patient in the monotherapy arm achieved a complete response. Median PFS in the combination arm was 11.0 months (95 percent CI, 5.45-13.63), versus 5.6 months (95 percent CI, 4.34-7.36) in the monotherapy arm. Grade three or higher TRAEs were observed in 45.5 percent of patients who received Balversa and cetrelimab combination therapy and 46.5 percent of patients who received Balversa monotherapy.
Results from the Phase II RAGNAR Study Evaluating the Efficacy and Safety of Balversa: Additionally, data from the phase II RAGNAR study, evaluating the efficacy and safety of Balversa in patients with advanced or metastatic solid tumors with prespecified FGFR alterations, regardless of tumor location or histology (tumor-agnostic), were also presented at ASCO this year. Treatment with Balversa demonstrated a clinically meaningful response at a median follow-up of 17.9 months, with an ORR of 30 percent (95 percent CI, 24-36). Responses were observed across 16 distinct tumors. Among the 64 responding patients, three percent of patients had a complete response and 27 percent of patients had a partial response. Grade three or higher TRAEs were observed in 46 percent of patients who received Balversa. Serious TRAEs were observed in 8.3 percent of patients and no deaths due to TRAEs were observed.
Balversa received accelerated approval from the FDA as a targeted therapy for adult patients with locally advanced or mUC with susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.