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

Other illness

• Any ocular condition likely to increase the risk of eye toxicity.
• History of or current uncontrolled cardiovascular disease.
• Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300.

Lab values

• Has a serum phosphorus level \> upper limit of normal (ULN) during screening that remains \>ULN despite medical management.

Other

• Active, symptomatic, or untreated brain metastases.
• Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

• 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.