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

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

This study is testing a new drug called TYRA-430 to see if it can help people with advanced liver and other solid tumors that have certain genetic changes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tyra Biosciences, Inc (Industry-sponsored)
• Drugs / interventions: immunotherapy
• Locations: 16 sites (Los Angeles, California and 15 other locations)
• Trial ID: NCT06915753 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced hepatocellular carcinoma or other solid tumors that have documented FGF/FGFR pathway alterations.

Not a fit: Patients with tumors that do not have FGF/FGFR pathway aberrations or those who are not eligible for the specified inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced liver and solid tumors that currently have limited treatment options.

How similar studies have performed: Other studies targeting FGFR pathways have shown promise, indicating that this approach may be beneficial, although this specific treatment is novel.

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.

Where this trial is running

Los Angeles, California and 15 other locations

• 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)
• Karmanos Cancer Institute — Detroit, Michigan, United States (Recruiting)
• Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
• Sarah Cannon Research Institute Oncology Partners — Nashville, Tennessee, United States (Recruiting)
• University Health Network Princess Margaret Cancer Center — Toronto, Ontario, Canada (Recruiting)
• Asan Medical Center — Seoul, South Korea (Recruiting)
• Samsung Medical Center — Seoul, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, South Korea (Recruiting)
• Severance Hospital, Yonsei University Health System — Seoul, South Korea (Recruiting)
• National Taiwan University Hospital — Taipei, Taiwan (Recruiting)
• Taipei Veterans General Hospital — Taipei, Taiwan (Recruiting)

Study contacts

• Study coordinator: Grace Indyk

Conditions Metastatic Hepatocellular Carcinoma; Solid Tumors; Solid Tumor, Adult; FGFR Gene Amplification; FGFR Gene Alterations; FGFR3 Gene Alteration; FGFR3 Gene Mutation; Advanced Solid Tumors