NCT06915753 Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
| NCT ID | NCT06915753 |
| Status | Recruiting |
| Phase | Phase 1 |
| Sponsor | Tyra Biosciences, Inc |
| Condition | Metastatic Hepatocellular Carcinoma |
| Study Type | INTERVENTIONAL |
| Enrollment | 100 participants |
| Start Date | 2025-04-24 |
| Primary Completion | 2028-01 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 100 participants in total. It began in 2025-04-24 with a primary completion date of 2028-01.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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, including locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors.
Eligibility Criteria
Key Inclusion Criteria: 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 Criteria: 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: 1. Any immunotherapy or other antibody therapy within 28 days prior to the first dose of the study drug. 2. A TKI \< 5 days or 5X the terminal Phase elimination half-lives, whichever is longer, prior to the first dose of TYRA-430. 3. 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.
Contact & Investigator
Doug Warner, MD
STUDY CHAIR
Tyra Biosciences, Inc
Frequently Asked Questions
Who can join the NCT06915753 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Metastatic Hepatocellular Carcinoma. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT06915753 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT06915753 currently recruiting?
Yes, NCT06915753 is actively recruiting participants. Contact the research team at TyraClinicalTrials@tyra.bio for enrollment information.
Where is the NCT06915753 trial being conducted?
This trial is being conducted at Los Angeles, United States, San Francisco, United States, Stanford, United States, Westwood, United States and 11 additional locations.
Who is sponsoring the NCT06915753 clinical trial?
NCT06915753 is sponsored by Tyra Biosciences, Inc. The principal investigator is Doug Warner, MD at Tyra Biosciences, Inc. The trial plans to enroll 100 participants.
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