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

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.