Mass General - Division of Clinical Research

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.

• 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.