medwireNews: Phase 2 trial findings demonstrate potential for the first-line use of rogaratinib plus atezolizumab in cisplatin-ineligible patients with advanced urothelial carcinoma (UC) with fibroblast growth factor receptor (FGFR)1–3 mRNA overexpression or FGFR3 mutations.
Jonathan Rosenberg, from Memorial Sloan Kettering Cancer Center in New York, USA, reported the open-label FORT-2 study safety and efficacy results in a poster at the 2021 ASCO Annual Meeting.
The maximum tolerated doses for the pan-FGFR and PD-L1 inhibitor combination were previously determined to be oral rogaratinib 600 mg twice daily plus atezolizumab 1200 mg given intravenously every 21 days, he explained.
At the time of data cutoff, 26 patients aged a median of 76 years had received the treatment, the majority of whom had metastatic diseases (81%), and low or no PD-L1 expression (77%). All patients had FGFR1–3 mRNA overexpression and/or FGFR3-activating mutations or translocations.
The presenter said that rogaratinib plus atezolizumab had a “manageable safety profile” that was “consistent” with earlier reports for the combination.
All patients experienced at least one treatment-emergent adverse event (TEAE), most commonly grade 1–2 diarrhea, hyperphosphatemia, nausea, and fatigue. Rogaratinib was associated with grade 2 retinal pigment epithelium detachment in one patient and grade 1–2 hyperphosphatemia in 58% of patients.
The most common grade 3–4 TEAEs were increased lipase without pancreatitis (19%), elevated amylase (12%), and rash (8%). TEAEs led to discontinuation of treatment in 23% of patients but “no pattern was seen,” Rosenberg commented, adding that 65% of patients had their treatment interrupted and 42% required a dose reduction. There were three deaths, all thought unrelated to treatment.
Of the 24 evaluable patients, 58% had a confirmed objective response to treatment, including three complete responses, and the disease control rate was 83%. The median duration of response was unreached after a median follow-up of 7.4 months and five responding patients are continuing with treatment.
Among 23 patients assessed for tumor response who underwent DNA sequencing, two patients had an FGFR3 mutation and both achieved an objective response. By contrast, objective responses did not occur in the one patient with a PIK3CA mutation or a second patient with a KRAS mutation.
Of note, 79% of the 14 patients with a response had low or negative PD-L1 expression. And further analysis of 16 patients with low or no PD-L1 expression and no FGFR3 mutation or fusion gave an objective response rate of 56% in this subgroup, comprised of two complete and seven partial responses.
This finding demonstrates “promising efficacy regardless of PD-L1 expression or FGFR3 mutation or fusion status,” Rosenberg stated.
The researchers conclude that their findings “warrant further investigation of rogaratinib plus atezolizumab in untreated patients with FGFR-positive, locally advanced or metastatic UC.”
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany
2021 ASCO Annual Meeting; 4–8 June