A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers with FGF/FGFR pathway aberrations, including locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors.
This is an open-label, multi-center, first-in-human, Phase 1 global study of TYRA-430, a first-in-class, selective, reversible fibroblast growth factor receptor (FGFR) 4 and 3 inhibitor, in locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors that contain FGF/FGFR pathway aberrations.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Oral TYRA-430 given daily.
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGUCSF Medical Center at Mount Zion
San Francisco, California, United States
RECRUITINGStanford Cancer Institute
Stanford, California, United States
RECRUITINGThe University of Kansas Medical Center
Westwood, Kansas, United States
RECRUITINGJohn Hopkins University
Baltimore, Maryland, United States
RECRUITINGMass General Cancer Center
Boston, Massachusetts, United States
RECRUITINGKarmanos Cancer Institute
Detroit, Michigan, United States
RECRUITINGColumbia University Irving Medical Center
New York, New York, United States
RECRUITINGSarah Cannon Research Institute Oncology Partners
Nashville, Tennessee, United States
RECRUITINGUniversity Health Network Princess Margaret Cancer Center
Toronto, Ontario, Canada
RECRUITING...and 6 more locations
Maximum tolerated dose (MTD)
MTD determination: dose limiting toxicity (DLT) rate in the first 28-day cycle
Time frame: Up to 1 year
Rate and severity of adverse events of TYRA-430 as monotherapy
Number of participants with TEAEs as assessed by CTCAE, v5.0
Time frame: First dose of study drug through 28 days after the last dose of study drug
Recommended Phase 2 dose(s) of TYRA-430
To determine recommended Phase 2 dose(s) of TYRA-430
Time frame: Up to 2 years
Cmax
Time frame: Up to 2 years
Tmax
Time frame: Up to 2 years
AUC0-last
Time frame: Up to 2 years
AUCTau
Time frame: Up to 2 years
AUC0-∞
Time frame: Up to 2 years
Vd/F
Time frame: Up to 2 years
CL/F
Time frame: Up to 2 years
t1/2
Time frame: Up to 2 years
Overall Response Rate (ORR)
The proportion of patients who experience a best response of confirmed CR or PR per RECIST 1.1
Time frame: Up to 3.5 years
Duration of Response (DOR)
Time from first investigator-assessed response to radiographic disease progression or death.
Time frame: Up to 3.5 years
Disease Control Rate (DCR)
Best response of CR, PR, or SD per RECIST v1.1 \> 12 months.
Time frame: Up to 3.5 years
Time to Response (TTR)
The median time from the start of therapy to first response in confirmed responders.
Time frame: Up to 3.5 years
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