Investigational FGFR3-Selective Inhibitor Shows Promise in Urothelial Cancer
TYRA-300 showed promising safety and preliminary antitumor activity in FGFR3-altered metastatic urothelial cancer, with a 54.5% partial response rate and 100% disease control in the SURF301 trial.
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TYRA-300, a new treatment for patients with metastatic urothelial cancer harboring FGFR3 alterations, is showing promise, according to data from the ongoing phase 1/2 SURF301 trial (NCT05544552).1
The investigational oral therapy, TYRA-300, is the first FGFR3-selective inhibitor in development, with early results suggesting both safety and antitumor activity.
In the SURF301 study, patients with FGFR3-altered metastatic urothelial cancer treated with TYRA-300 at doses of at least 90 mg per day demonstrated a 54.5% partial response (PR) rate.
Notably, 3 of the 6 responses were still ongoing at the data cutoff date of August 15, 2024, highlighting potential durability. The overall disease control rate among patients treated at this dose level was 100%.
The majority of patients in this study (n = 10) received 90 mg daily, with a PR rate of 50% observed within this subgroup. Additionally, 1 patient receiving a higher dose of 120 mg daily also demonstrated a PR.
TYRA-300 has shown to be well tolerated overall. Adverse effects typical of pan-FGFR inhibitors, such as FGFR1 and FGFR2 toxicities, were not frequently observed. Ten percent of patients treated across TYRA-300 dose ranges of 10 mg to 120 mg daily reported serious treatment-related adverse effects (TRAEs). These included 1 case of grade 3 diarrhea at the 90-mg dose and 1 case of grade 3 elevated alanine aminotransferase, leading to treatment discontinuation.
"FGFR3 alterations are known to drive tumor biology in a subset of urothelial cancer.While pan-FGFR inhibitors have demonstrated benefit and are approved for use in FGFR3-altered urothelial cancer, they are associated with multiple intolerable on-target toxicities that limit their clinical utility.There remains an unmet need to deliver improved precision medicine for urothelial cancer patients, that allow patients to not only live longer, but live better," said Ben Tran, MD, associate professor, Peter MacCallum Cancer Centre, Melbourne, Australia, in a press release.
As of the most recent data update, pharmacokinetic analysis from 41 patients also showed adequate FGFR3 target coverage at doses of 90 mg daily or higher, suggesting that this dose is likely optimal for achieving the desired therapeutic effect.
"The initial results from TYRA-300 are very encouraging. I believe TYRA-300 has the potential to be a next generation targeted therapy, with high selectivity for FGFR3. These early data provide support that TYRA-300 can deliver improved antitumor activity and tolerability for our FGFR3-altered urothelial cancer patients. TYRA-300 has real potential to improve outcomes, and I look forward to its continued development in all FGFR3-altered cancers." Tran continued.
About the SURF301 Trial
The SURF301 trial is a single-arm, multipart study evaluating TYRA-300 across various solid tumors with FGFR3 alterations.2 The phase 1 component includes patients with advanced solid tumors who have exhausted standard-of-care options. In phase 1 part B, patients are required to have advanced solid tumors with FGFR3 mutations.
Phase 2 of the study is focused on patients with FGFR3-altered urothelial carcinoma who have either developed resistance to a prior FGFR inhibitor or have not yet received one, as well as other patients with solid tumors harboring FGFR3 mutations.
In part A of phase 1, TYRA-300 was evaluated at daily doses from 10 mg to 120 mg, with the primary end point of identifying the maximum tolerated dose. Part B’s primary end point is to further refine the recommended phase 2 dose, which will be used to assess the overall response rate in phase 2.
