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.
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.
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.
Sequential
Phase 1 Part A - dose escalation TYRA-200 taken once daily by mouth in 28-day cycles
DrugTYRA-200 is an oral, novel potent FGFR 1/2/3 tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR2.
Phase 1 Part B - dose expansion TYRA-200 taken once daily by mouth in 28-day cycles
DrugTYRA-200 is an oral, novel potent FGFR 1/2/3 tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR2.
Phase 1 Part A: To determine the maximum tolerated dose (MTD) of TYRA-200.
Phase 1 Part B: To determine the optimal dose of TYRA-200.
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
Frequency in changes in laboratory parameters and physical signs of toxicity.
Pharmacokinetics: maximum plasma concentration (Cmax).
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
Click on the lead sponsor to view all of their trials.
