Safety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-200 in cancers with FGFR2 activating gene alterations, including unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors.

Inclusion Criteria: Phase 1 Part A * Men and women 18 years of age or older. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1. * Any histologically confirmed advanced solid tumor with FGFR/FGF pathway alterations including FGFR gene mutations, fusions, and amplifications, as well as gene amplifications of FGFR ligands, who have exhausted or refused approved standard therapies. * Evaluable disease according to RECIST v1.1. Phase 1 Part B * Men and women 18 years of age or older. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1. * Histologically confirmed locally advanced/metastatic intrahepatic cholangiocarcinoma with a previously identified FGFR2 gene mutation or rearrangement. * Must have received a prior FGFR inhibitor. Participants may have received more than 1 prior FGFR inhibitor. * Presence of an FGFR2 kinase domain mutation that confers resistance to previous/other FGFR inhibitors; resistance mutations should be identified by a US Food and Drug Administration authorized/approved companion diagnostic or a Clinical Laboratory Improvement Amendments (CLIA) validated local test performed in a certified laboratory. * At least 1 measurable lesion by RECIST v1.1. Exclusion Criteria: * Discontinued a prior anti-FGFR therapy due to significant toxicity, defined as hepatotoxicity ≥Grade 3 or any Grade 4 toxicity according to CTCAE v5.0. * 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-200. * Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.