In the phase Ib FORT-2 trial reported in JAMA Oncology, Sweis et al found that the combination of the pan-FGFR inhibitor rogaratinib and atezolizumab was active in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer overexpressing FGFR mRNA.
Study Details
The study included 37 patients with tumors with FGFR1/3 mRNA overexpression enrolled between May 2018 and July 2021 from sites in Asia, Europe, and North America. Patients received rogaratinib at 600 mg (n = 26) or 800 mg (n = 11) twice daily with atezolizumab at 1,200 mg every 21 days.
Key Findings
Among the 37 patients, objective responses were observed in 16 (43%), with disease control achieved in 24 (65%). The most common adverse events of any grade were diarrhea (62%), hyperphosphatemia (51%), and fatigue (41%). Grade ≥ 3 adverse events were reported in 27 patients (73%). No treatment-related deaths were observed. Adverse events leading to rogaratinib discontinuation were less common among patients receiving the 600 mg dose (7/26 = 27%) compared with those receiving 800 mg (6/11 = 55%).
The recommended phase II dose was rogaratinib at 600 mg twice daily plus atezolizumab at 1,200 mg. At this dose, objective response was observed in 14 (53.8%) of 26 patients, including complete response in 4 (15%). Among the 14 patients with objective response, 12 did not have FGFR3 gene alteration and 11 (79%) had low PD-L1 expression. Median duration of response was not reached at study completion and some complete responses were ongoing. The disease control rate was 76.9%.
Median progression-free survival was 7.5 months (95% confidence interval [CI] = 4.0 months to not estimable) among patients receiving rogaratinib at 600 mg and 2.1 months (95% CI = 1.0-2.2 months) among patients receiving rogaratinib at 800 mg. 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.
The investigators concluded: “In this phase Ib nonrandomized clinical trial, rogaratinib plus atezolizumab demonstrated a manageable safety profile, with no unexpected safety signals. Efficacy for this combination at the [recommended phase II dose] was observed in tumors with low PD-L1 and was not dependent on FGFR3 gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic [urothelial cancer] and FGFR mRNA overexpression.”
Randy F. Sweis, MD, of the University of Chicago Medicine, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by the National Cancer Institute and by Bayer. For full disclosures of the study authors, visit jamanetwork.com.
