Infigratinib Demonstrates Activity and Tolerability of FGFR Inhibition in Urothelial Carcinoma

Interim results from a biomarker-informed preoperative study of infigratinib (Truseltiq), an oral inhibitor of FGFR1-3, demonstrated substantial activity and tolerability in patients with localized upper tract urothelial carcinoma (UTUC), according to findings of a phase 1b trial (NCT04228042).

A total of 12 patients with FGFR3 mutations were enrolled, with 11 patients deemed evaluable, according to investigators. Nine patients completed therapy and 2 continued on treatment as of the data cutoff; however, 2 patients experienced toxicities that resulted in dose reductions and 2 patients discontinued treatment. One patient discontinued treatment because of fatigue, and one patient discontinued because of liver injury. Four of 9 patients (44%) who completed therapy showed tumor reduction that ranged from 25% to 83%. From a clinical perspective, 2 patients who were scheduled to undergo nephroureterectomy were able to be treated through endoscopic management.

Surena F. Matin, MD, the Monteleone Family Foundation Distinguished Professor with Tenure in the Department of Urology at The University of Texas MD Anderson Cancer Center, Houston, presented findings during the 2022 American Urology Association Annual Meeting.¹ Investigators reported that all responders had FGFR3 mutations and that most non-responders had a prior history of bladder cancer, with 1 patient having a FGFR3-TACC3 fusion. Four patients who were biomarker negative did not have a response.

Patients with low-grade or localized cisplatin ineligible high-grade UTUC who were candidates for either ureteroscopic (URS) management or nephrourectomy/ureterectomy (NU/U) were enrolled from May 2021 to February 2022. Eligibility requirements included having a glomerular filtration rate of 30 or greater, sufficient biopsy tissue that could be used for mutational analysis, and a tumor map for residual tumors after biopsy and ablation. Patients were ineligible if they had a primary malignancy within 3 years, had uncontrolled bladder cancer, or had impaired gastrointestinal function that affects the absorption of oral infigratinib.

Patients received 2 cycles of 125 mg of oral infigratinib for 21 days of a 28-day cycle. After completing the second cycle, patients underwent tumor mapping based on URS or NU/U. The primary end point was tolerability and the secondary end points were objective response based on tumor mapping, circulating cell-free DNA analysis, expression of markers, and FGFR3 alteration type. Targeted sequencing was conducted using a NovaSeq 6000 solid tumor panel accounting for 610 somatic alterations including 33 fusions.

Previously, infigratinib had demonstrated activity in patients with metastatic urothelial cancer (response rate [RR], 25.4%), specifically in patients with metastatic UTUC (RR, 50%).² A phase 2 expansion study that evaluates additional cycles of the agent is underway.

REFERENCES

Matin S, Adibi M, Shah A, et al. Interim Results from a Phase 1b Clinical Trial Evaluating Tolerability and Activity of FGFR Inhibition in Localized Upper Tract Urothelial Carcinoma (UTUC). Presented at: 2022 American Urology Association Annual Meeting; May 13-16, 2022; New Orleans, LA. Abstract OBA01-10. Accessed May 15, 2022. https://bit.ly/3PlWwFW

Dizman N, Rosenberg JE, Hoffman-Censits JHH, et al. Infigratinib in upper tract urothelial carcinoma vs urothelial carcinoma of the bladder and association with comprehensive genomic profiling/cell-free DNA results. J Clin Oncol. 2019;37(suppl 15):4510. doi:10.1200/JCO.2019.37.15_suppl.4510