A Multicenter, Open-label Phase 1/2 Study of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors with Activating FGFR3 Gene Alterations (SURF-301)
Trial Description
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and
preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations,
including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract
and other advanced solid tumors.
Eligibility Requirements
Inclusion Criteria:
Phase 1 Part A and Part B
- Men and women 18 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- Histologically confirmed advanced solid tumor who have exhausted standard therapeutic
options.
- Evaluable (Part A) or measurable (Part B) disease according to RECIST v1.1.
- Histologically confirmed advanced solid tumor with an eligible FGFR3 gene mutation or
fusion (Part B).
Phase 2
- Men and women 18 years of age or older.
- ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70.
- At least 1 measurable lesion by RECIST v1.1.
- Histologically confirmed locally advanced/metastatic tumor in one of the following
categories:
- Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who
have progressed on a prior FGFR inhibitor and presence of a resistance mutation
or other kinase domain mutation.
- Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who
has not received a prior FGFR inhibitor.
- Any solid tumor with an eligible FGFR3 gene mutation or rearrangement.
Exclusion Criteria (All Phases):
- Has a serum phosphorus level > upper limit of normal (ULN) during screening that
remains >ULN despite medical management.
- Any ocular condition likely to increase the risk of eye toxicity.
- History of or current uncontrolled cardiovascular disease.
- Active, symptomatic, or untreated brain metastases.
- Gastrointestinal disorders that will affect oral administration or absorption of
TYRA-300.
- Females who are pregnant, breastfeeding, or planning to become pregnant and males who
plan to father a child while enrolled in this study.