Activation of FGFR signaling is involved in a variety of malignancies including advanced urothelial cancer.
Rogaratinib is an oral pan-FGFR kinase inhibitor.
Results from a phase I expansion cohort in patients with urothelial cancer prescreened for FGFR1-3 mRNA expression levels and activating mutations, were presented.
Patients with advanced urothelial carcinomas were selected based on high FGFR1-3 mRNA expression in biopsy specimens.
Selected patients were treated with Rogaratinib 800mg twice daily until tumour progression, untolerable toxicity, or withdrawal.
Tumor response was assessed by RECIST, v1.1.
Adverse events were reported using CTCAE v4.03 criteria.
A total of 219 patients with urothelial cancer were prescreened for FGFR1-3 mRNA expression levels and FGFR3 activating mutations, with 99 samples ( 45% ) found to be FGFR-positive.
Of those, 87% of samples were positive for FGFR3 mRNA, 5% for FGFR1 mRNA and 8% were double FGFR mRNA-positive ( FGFR1/2, 1/3 or 2/3 ).
Frequency of FGFR3 activating mutations in urothelial cancer samples was 7%, all of which also had high FGFR3 mRNA.
Fifty two patients ( median prior line of treatment 2 ) started treatment and 51 were evaluable for response.
Rogaratinib was generally well tolerated and AEs manageable with dose modification. The most common adverse effects were diarrhea ( 49% ) and hyperphosphatemia ( 49% ).
Objective response rate ( ORR ) was 24% ( 12/51; all PRs ) and disease control rate ( DCR ) was 73% ( 37/51 ).
Eleven of 12 pts with a partial response ( PR ) were positive for FGFR3 mRNA, 5 of whom also had FGFR3 mutations, and one patient was positive for FGFR1 mRNA.
Ten FGFR-positive patients with urothelial cancer had prior immuno-oncology treatment, 9 of whom had progressive disease as best response.
For these 10 patients the ORR was 30% and the DCR 80%.
In conclusion, selection of patients for treatment with Rogaratinib based on FGFR mRNA expression levels was feasible and identified drug-sensitive patients with and without underlying DNA alterations.
Rogaratinib had a favorable safety profile and showed promising anti-tumor activity in patients with urothelial cancer.
Responses and disease stabilization were observed with Rogoratinib in patients with urothelial cancer refractory to prior immuno-oncology treatment. ( Xagena )
Source: Journal of Clinical Oncology, 2018