Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations

Inclusion Criteria

• 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.