We initiated a biomarker-informed preoperative study of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations.
Materials and Methods:
Patients with localized UTUC undergoing ureteroscopy or nephroureterectomy/ureterectomy were enrolled on a phase 1b trial (NCT04228042). Once-daily infigratinib 125 mg by mouth × 21 days (28-day cycle) was given for 2 cycles. Tolerability was monitored by Bayesian design and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, done after endoscopic biopsy and post-trial surgery. Total planned enrollment: 20 patients. Targeted sequencing performed using a NovaSeq 6000 solid tumor panel.
Results:
From May 2021 to November 2022, 14 patients were enrolled, at which point the trial was closed due to termination of all infigratinib oncology trials. Two patients (14.3%) had treatment-terminating toxicities, well below the stopping threshold. Responses occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had median tumor size reduction of 67%, with 3 of 5 patients initially planned for nephroureterectomy/ureterectomy converted to ureteroscopy. Median follow-up in responders was 24.7 months (14.9-28.9).
Conclusions:
In this first trial of targeted therapy for localized UTUC, FGFR inhibition was well tolerated and had significant activity in FGFR3 altered tumors. Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs.
- Surena F. Matin, MD, Department of Urology, MD Anderson Cancer Center, Houston, TX
- Mehrad Adibi, Department of Urology, MD Anderson Cancer Center, Houston, Texas
- Amishi Y. Shah, Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, Texas
- Omar Alhalabi, Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, Texas
- Paul Corn, Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, Texas
- Charles Guo, Department of Pathology, MD Anderson Cancer Center, Houston, Texas
- Rhenita Amirtharaj, Department of Urology, MD Anderson Cancer Center, Houston, Texas
- Lianchun Xiao, Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas
- Suzanne Lange, Department of Urology, MD Anderson Cancer Center, Houston, Texas
- Dzifa Y. Duose, Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas
- Shufang Wang, Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas
- Sumanta Pal, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California
- Matthew T. Campbell, Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, Texas
Matin SF, Adibi M, Shah AY, Alhalabi O, Corn P, Guo C, et al. Phase 1b Trial Evaluating Tolerability and Activity of Targeted Fibroblast Growth Factor Receptor Inhibition in Localized Upper Tract Urothelial Carcinoma. Journal of Urology [Internet]. 2024 Jun 1 [cited 2024 Jul 10];211(6):784–93. Available from: https://doi.org/10.1097/JU.0000000000003928