Metastatic Hepatocellular CarcinomaPhase 1SURF431NCT06915753
Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
A Phase 1 study testing TYRA-430 in people with Metastatic Hepatocellular Carcinoma and Solid Tumors, run by Tyra Biosciences, Inc at 16 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Hepatocellular Carcinoma, Solid Tumors, Solid Tumor, Adult
- What is being tested?
- TYRA-430
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 16 sitesin 4 countries
- Study dates
- 24 Apr 2025to Sep 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Patients:
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- Adequate end organ function.
- Ability to swallow oral formulations.
- Ability to understand and willingness to sign the ICF.
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- Part A:
- Histologically confirmed locally advanced unresectable/metastatic HCC or histologically confirmed advanced solid tumor with documented FGF/FGFR pathway alterations
- For participants with histologically confirmed locally advanced or metastatic HCC:
- Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.
- Child-Pugh Score class A
- Must have previously received SOC appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted.
- Agree to provide archival tumor tissue, if available. If an archived specimen is not available, a biopsy is not required.
- Part B, Cohort 1:
- Histologically confirmed locally advanced/metastatic HCC who have previously received standard of care.
- Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.
- Child-Pugh Score class A
- Availability of an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen for submission to sponsor-designated central laboratory for FGF19 IHC testing.
- At least 1 measurable lesion by RECIST v1.1.
- Part B, Cohort 2:
- Histologically confirmed advanced solid tumor except FGFR3-altered urothelial carcinoma and primary central nervous system tumors who have previously received standard of care. Note: Participants with confirmed diagnosis of locally advanced or metastatic HCC are not eligible for Cohort 2.
- Must have an eligible activating gain-of-function alteration in the FGFR4 gene, or focal amplifications of FGF19
- Archival tumor tissue biopsy specimen , if available. If a tissue biopsy specimen is not available, a biopsy is not required.
- At least 1 measurable lesion by RECIST v1.1.
Who cannot join
- All Patients:
- Have disease that is suitable for local therapy administered with curative intent.
- Have not recovered from reversible toxicity of prior anticancer therapy to < Grade 1 or baseline (except toxicities that are not clinically significant or not expected to resolve, including but not limited to, alopecia, fatigue, skin discoloration, or Grade 1 neuropathy).
- Have received the following anticancer therapy:
- Any immunotherapy or other antibody therapy within 28 days prior to the first dose of the study drug.
- A TKI < 5 days or 5X the terminal Phase elimination half-lives, whichever is longer, prior to the first dose of TYRA-430.
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- Other systemic therapy not listed above < 14 days prior to the first dose of the study drug.
- Participant discontinued a prior anti-FGFR therapy due to significant toxicity
- Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
- History of or current uncontrolled cardiovascular disease.
- Active, symptomatic, or untreated brain metastases.
- Have a diagnosis of primary CNS malignancies.
- Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430.
- Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.
- Any reason that, in the view of investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant.
- Part B, Cohort 1:
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors.
- Part B, Cohort 2:
- Histologically confirmed locally advanced/metastatic HCC.
- Histologically confirmed urothelial cancer.
Trial locations and contacts
16 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
16 sites in 4 countries
United States9 sites, 8 recruiting
- Recruiting
John Hopkins University
Baltimore, Maryland, 21205
- Recruiting
Mass General Cancer Center
Boston, Massachusetts, 02114
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
- Withdrawn
Sarah Cannon Research Institute Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10043
- Recruiting
UCSF Medical Center at Mount Zion
San Francisco, California, 94158
- Recruiting
Stanford Cancer Institute
Stanford, California, 94305
- Recruiting
The University of Kansas Medical Center
Westwood, Kansas, 66205
South Korea4 sites, 4 recruiting
- Recruiting
Asan Medical Center
Seoul
- Recruiting
Samsung Medical Center
Seoul
- Recruiting
Seoul National University Hospital
Seoul
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul
Taiwan2 sites, 2 recruiting
- Recruiting
National Taiwan University Hospital
Taipei
- Recruiting
Taipei Veterans General Hospital
Taipei
Canada1 site, 1 recruiting
- Recruiting
University Health Network Princess Margaret Cancer Center
Toronto, Ontario, M5G 2C4
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Metastatic Hepatocellular Carcinoma, Solid Tumors, Solid Tumor, Adult, FGFR Gene Amplification, FGFR Gene Alterations, Advanced Solid Tumors
- Being tested
- TYRA-430
- Keywords
- Hepatocellular Carcinoma, metastatic cancer, solid tumors, FGF19 gene amplifications, FGFR4 gene alterations, FGF19 gene alterations, FGFR4 gene mutations, FGFR4 gene fusions, FGF19 gene overexpression, locally advanced unresectable cancer
- Medical subject headings
- Carcinoma, Hepatocellular, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TYRA-430Drug
Oral TYRA-430 given daily.
| Study group | Role | What they receive |
|---|---|---|
| Part A - Dose Escalation | Experimental | Dose escalation of TYRA-430 as monotherapy at various dose levels. Receives: Drug: TYRA-430 |
| Part B - Cohort 1 Dose Expansion | Experimental | Dose expansion group for TYRA-430 monotherapy in advanced HCC at a dose(s) determined in Part A. Receives: Drug: TYRA-430 |
| Part B - Cohort 2 Dose Expansion | Experimental | Dose expansion group for TYRA-430 monotherapy in advanced solid tumors at a dose(s) determined in Part A. Receives: Drug: TYRA-430 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
MTD determination: dose limiting toxicity (DLT) rate in the first 28-day cycle
Measured: 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
Measured: 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
Measured: Up to 2 years
Secondary outcomes (12)
Cmax
Measured: Up to 2 years
Tmax
Measured: Up to 2 years
AUC0-last
Measured: Up to 2 years
AUCTau
Measured: Up to 2 years
AUC0-∞
Measured: Up to 2 years
Vd/F
Measured: Up to 2 years
CL/F
Measured: Up to 2 years
t1/2
Measured: 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
Measured: Up to 3.5 years
Duration of Response (DOR)
Time from first investigator-assessed response to radiographic disease progression or death.
Measured: Up to 3.5 years
Disease Control Rate (DCR)
Best response of CR, PR, or SD per RECIST v1.1 > 12 months.
Measured: Up to 3.5 years
Time to Response (TTR)
The median time from the start of therapy to first response in confirmed responders.
Measured: Up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2025
- Study start24 Apr 2025
- Primary completionJan 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tyra Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Doug Warner, MD, Study chair, Tyra Biosciences, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06915753
- Sponsor's protocol ID
- TYR430-101
- Acronym
- SURF431
- Status last verified
- Oct 2026
- First submitted
- 31 Mar 2025
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided