Status:
RECRUITING
Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
Lead Sponsor:
Tyra Biosciences, Inc
Conditions:
Metastatic Hepatocellular Carcinoma
Solid Tumors
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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, includin...
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 ad...
Eligibility Criteria
Inclusion
- Key
- 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.
- 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 no older than 2 years from the time of enrollment, 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 obtained ≤2 years prior to screening 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 FGFR3 or FGFR4 gene, or focal amplifications of FGF19
- Archival tumor tissue biopsy specimen no older than 2 years from the time of enrollment, if available. If a tissue biopsy specimen is not available, a biopsy is not required.
- At least 1 measurable lesion by RECIST v1.1.
- Key
Exclusion
- 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.
- 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, 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.
- 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.
Key Trial Info
Start Date :
April 24 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2028
Estimated Enrollment :
100 Patients enrolled
Trial Details
Trial ID
NCT06915753
Start Date
April 24 2025
End Date
September 1 2028
Last Update
November 20 2025
Active Locations (16)
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1
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
2
UCSF Medical Center at Mount Zion
San Francisco, California, United States, 94158
3
Stanford Cancer Institute
Stanford, California, United States, 94305
4
The University of Kansas Medical Center
Westwood, Kansas, United States, 66205