Introduction: Infigratinib is a potent oral inhibitor of FGFR1-3 with activity in metastatic urothelial cancer (response rate [RR], 25.4%), particularly in patients with metastatic UTUC (RR 50%) (Dizman et al ASCO 2020). We initiated a biomarker-informed preoperative study of infigratinib in patients with localized UTUC.
Methods: Patients with low-grade, or localized cis-platin ineligible high-grade UTUC, undergoing either ureteroscopic (URS) management or nephroureterectomy/ureterectomy (NU/U), were enrolled on a preoperative phase 1b trial (NCT04228042). Enrollment required a GFR of 30 or greater, sufficient biopsy tissue for mutational analysis, and a tumor map of all residual tumors after endoscopic biopsy and any ablation. Treatment consisted of once-daily infigratinib 125 mg (21 days of 28-day cycle) for 2 cycles. A second tumor map based on URS or NU/U was completed after cycle 2. Tolerability was assessed by ongoing monitoring and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, with a total planned enrollment of 20 patients. Targeted sequencing was performed using a NovaSeq 6000 solid tumor panel covering 610 somatic alterations including 33 fusions.
Results: From May 2021 until Feb 2022, 12 patients were enrolled (Table). Of 11 evaluable patients, 9 completed therapy and 2 continue on treatment. Of the 9 patients completing therapy, 2 had toxicities preventing the full duration of treatment. 4 of 9 (44%) patients had a response with tumor reduction (range 25-83%); all responders had FGFR3 mutations. Most non-responders had a prior history of bladder cancer and 1 had FGFR3-TACC3 fusion.
Conclusions: Infigratinib shows substantial activity in patients with localized UTUC bearing FGFR3 mutations, consistent with previous data in the metastatic setting. Enrollment continues, and based on these promising initial results, a phase 2 expansion evaluating additional cycles is planned.
Source of Funding: The trial was sponsored by QED Therapeutics. Sponsor had no involvement with data acquisition, analysis, or drafting of abstract.