Actively Recruiting
A Multicenter, Open-label, First-in-Human Study of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
Led by Tyra Biosciences, Inc · Updated on 2025-11-20
100
Participants Needed
16
Research Sites
34 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating TYRA-430, a selective and reversible inhibitor of fibroblast growth factor receptors 3 and 4, in people with locally advanced or metastatic hepatocellular carcinoma and other advanced solid tumors that have abnormalities in the FGF/FGFR pathway. This first-in-human, open-label, Phase 1 study aims to assess the safety, tolerability, how the drug moves and acts in the body, and preliminary anti-tumor effects of TYRA-430. Participants will receive oral TYRA-430 daily in a dose escalation phase to find the best dose. After this, two dose expansion groups will receive the drug at the selected dose: one with advanced hepatocellular carcinoma and another with other advanced solid tumors showing specific genetic changes. The study is non-randomized and open-label, meaning all participants know they are receiving the drug. During the study, participants will be monitored for adverse events and dosing tolerability up to a year, with longer follow-up for determining recommended doses and tumor response measures up to several years. Assessments include tumor imaging to measure response, laboratory tests, and other safety evaluations. The trial will last until around September 2028, and participants' health and tumor status will be regularly evaluated throughout.
CONDITIONS
Brief Title
Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- ECOG performance status of 0 or 1
- Adequate end organ function
- Ability to swallow oral medications
- Willingness and ability to sign informed consent
- Histologically confirmed locally advanced unresectable or metastatic hepatocellular carcinoma or advanced solid tumor with documented FGF/FGFR pathway alterations (Part A)
- For hepatocellular carcinoma: BCLC stage B (not eligible for locoregional therapy) or stage C, Child-Pugh Score class A
- Prior standard of care treatment appropriate for tumor type, including any number of prior therapies
- Agreement to provide archival tumor tissue no older than 2 years if available
- Histologically confirmed locally advanced/metastatic hepatocellular carcinoma who have received standard of care (Part B, Cohort 1)
- Availability of archival tumor tissue specimen for FGF19 testing (Part B, Cohort 1)
- At least 1 measurable lesion by RECIST v1.1 (Part B, Cohort 1 and 2)
- Histologically confirmed advanced solid tumor with activating FGFR3 or FGFR4 gene alterations or FGF19 focal amplifications, excluding urothelial carcinoma and CNS tumors (Part B, Cohort 2)
You will not qualify if you...
- Disease suitable for local therapy with curative intent
- Unresolved toxicity from prior anticancer therapy greater than Grade 1 except for non-significant toxicities
- Recent immunotherapy or antibody therapy within 28 days prior to study drug
- Recent tyrosine kinase inhibitors within 5 days or 5 times elimination half-life before study drug
- Other systemic therapy within 14 days prior to study drug
- Prior anti-FGFR therapy discontinued due to significant hepatotoxicity or Grade 4 toxicity
- Serum phosphorus level above upper limit of normal despite medical management
- History of or current uncontrolled cardiovascular disease
- Active, symptomatic, or untreated brain metastases
- Diagnosis of primary central nervous system malignancies
- Gastrointestinal disorders affecting oral drug administration or absorption
- Pregnant or breastfeeding females, or males planning to father a child during the study
- Any condition that impairs ability to comply with study procedures or increases risk
- Known fibrolamellar, sarcomatoid, or mixed cholangiocarcinoma and hepatocellular carcinoma (Part B, Cohort 1)
- Prior treatment with pan-FGFR or FGFR4-selective inhibitors (Part B, Cohort 1)
- Histologically confirmed locally advanced/metastatic hepatocellular carcinoma (Part B, Cohort 2)
- Histologically confirmed urothelial cancer (Part B, Cohort 2)
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 3.5 years
Participants receive oral TYRA-430 daily as part of dose escalation or dose expansion groups to evaluate safety and preliminary anti-tumor activity.
Regular visits at intervals determined by the study protocol during treatment
Trial Site Locations
Total: 16 locations
1
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Actively Recruiting
2
UCSF Medical Center at Mount Zion
San Francisco, California, United States, 94158
Actively Recruiting
3
Stanford Cancer Institute
Stanford, California, United States, 94305
Actively Recruiting
4
The University of Kansas Medical Center
Westwood, Kansas, United States, 66205
Actively Recruiting
5
John Hopkins University
Baltimore, Maryland, United States, 21205
Actively Recruiting
6
Mass General Cancer Center
Boston, Massachusetts, United States, 02114
Actively Recruiting
7
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Actively Recruiting
8
Columbia University Irving Medical Center
New York, New York, United States, 10043
Actively Recruiting
9
Sarah Cannon Research Institute Oncology Partners
Nashville, Tennessee, United States, 37203
Actively Recruiting
10
University Health Network Princess Margaret Cancer Center
Toronto, Ontario, Canada, M5G 2C4
Actively Recruiting
11
Asan Medical Center
Seoul, South Korea
Actively Recruiting
12
Samsung Medical Center
Seoul, South Korea
Actively Recruiting
13
Seoul National University Hospital
Seoul, South Korea
Actively Recruiting
14
Severance Hospital, Yonsei University Health System
Seoul, South Korea
Actively Recruiting
15
National Taiwan University Hospital
Taipei, Taiwan
Actively Recruiting
16
Taipei Veterans General Hospital
Taipei, Taiwan
Actively Recruiting
Research Team
G
Grace Indyk
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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