Evaluating TYRA-430 for advanced liver and solid tumors with specific genetic changes

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1 clinical trial aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of TYRA-430, a selective inhibitor targeting fibroblast growth factor receptors (FGFR) 3 and 4. The study focuses on patients with advanced hepatocellular carcinoma and other solid tumors that exhibit aberrations in the FGF/FGFR pathway. It is an open-label, multi-center trial that includes participants who have previously undergone standard of care treatments. The trial will evaluate the drug's effectiveness in patients with specific genetic alterations related to their tumors.

Why it matters

Who can join: the full rules

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, 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.

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
* 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.

Where it's running

• USC Norris Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• UCSF Medical Center at Mount Zion
  San Francisco, California, United States Recruiting
• Stanford Cancer Institute
  Stanford, California, United States Recruiting
• The University of Kansas Medical Center
  Westwood, Kansas, United States Recruiting
• John Hopkins University
  Baltimore, Maryland, United States Recruiting
• Mass General Cancer Center
  Boston, Massachusetts, United States Recruiting

Study contacts

• Study coordinator: Lara Balick
• Email: TyraClinicalTrials@tyra.bio
• Phone: 929-792-5633

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.