A phase Ib trial, FORT-2, has indicated that the combination of rogaratinib and atezolizumab demonstrates promising activity in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer that overexpresses FGFR mRNA. The study, published in JAMA Oncology, suggests a potential new treatment option for this patient population.
The nonrandomized clinical trial enrolled 37 patients with tumors exhibiting FGFR1/3 mRNA overexpression from May 2018 to July 2021 across multiple sites in Asia, Europe, and North America. Patients were administered rogaratinib at either 600 mg (n = 26) or 800 mg (n = 11) twice daily, in conjunction with atezolizumab at 1,200 mg every 21 days.
Efficacy and Safety Findings
The study revealed an objective response rate of 43% (16 out of 37 patients), with disease control achieved in 65% (24 patients). The most frequently reported adverse events of any grade included diarrhea (62%), hyperphosphatemia (51%), and fatigue (41%). Grade ≥ 3 adverse events were observed in 73% of patients (27 patients). Notably, no treatment-related deaths occurred. Discontinuation of rogaratinib due to adverse events was less frequent in the 600 mg dose group (27%) compared to the 800 mg dose group (55%).
Based on these findings, the recommended phase II dose was established as rogaratinib 600 mg twice daily plus atezolizumab 1,200 mg. At this dose, the objective response rate was 53.8% (14 out of 26 patients), including a complete response in 15% (4 patients). Among responders, the majority (12 patients) did not have FGFR3 gene alterations, and 79% (11 patients) had low PD-L1 expression. The median duration of response was not reached by study completion, with some complete responses ongoing. The disease control rate at this dose was 76.9%.
Survival Outcomes
Median progression-free survival was 7.5 months (95% CI = 4.0 months to not estimable) in the 600 mg rogaratinib group and 2.1 months (95% CI = 1.0-2.2 months) in the 800 mg group. Median overall survival was 16.8 months (95% CI = 12.0 months to not estimable) in the 600-mg group and 8.3 months (95% CI = 2.2–9.8 months) in the 800-mg group.
Clinical Implications
The investigators concluded that the combination of rogaratinib and atezolizumab demonstrated a manageable safety profile, with no unexpected safety signals. Efficacy at the recommended phase II dose was observed in tumors with low PD-L1 expression and was not dependent on FGFR3 gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic urothelial cancer and FGFR mRNA overexpression. According to Dr. Randy F. Sweis, MD, of the University of Chicago Medicine, the corresponding author for the JAMA Oncology article, this combination could offer a new treatment avenue for patients who are ineligible for cisplatin-based chemotherapy.
