Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations

NCT06915753 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TYR430-101
• Study Type: interventional
• Target: 100
• Locations: 4 countries
• Sites: 16

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.

Conditions

Metastatic Hepatocellular Carcinoma; Solid Tumors; Solid Tumor, Adult; FGFR Gene Amplification; FGFR Gene Alterations; FGFR3 Gene Alteration; FGFR3 Gene Mutation; Advanced Solid Tumors; FGFR4 Gene Mutation; FGFR4 Gene Fusions; FGF19 Gene Amplification; FGF19 Gene Overexpression; FGFR3 Gene Fusions; Locally Advanced Unresectable Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; metastatic cancer; solid tumors; FGF19 gene amplifications; FGFR4 gene alterations; FGFR3 gene alterations; FGF19 gene alterations; FGFR4 gene mutations; FGFR4 gene fusions; FGFR3 gene mutations; FGFR3 gene fusions; FGF19 gene overexpression; locally advanced unresectable cancer

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  MTD determination: dose limiting toxicity (DLT) rate in the first 28-day cycle

  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

  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

  Up to 2 years

Secondary Outcomes (12)

• Cmax

  Up to 2 years

• Tmax

  Up to 2 years

• AUC0-last

  Up to 2 years

• AUCTau

  Up to 2 years

• AUC0-∞

  Up to 2 years

Study Arms (3)

Part A - Dose Escalation

EXPERIMENTAL

Dose escalation of TYRA-430 as monotherapy at various dose levels.

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.

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.

Drug: TYRA-430

Interventions

TYRA-430 DRUG

Oral TYRA-430 given daily.

Part A - Dose Escalation; Part B - Cohort 1 Dose Expansion; Part B - Cohort 2 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tyra Biosciences, Inc: lead

Study Sites (16)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

UCSF Medical Center at Mount Zion

San Francisco, California, 94158, United States

RECRUITING

Stanford Cancer Institute

Stanford, California, 94305, United States

RECRUITING

The University of Kansas Medical Center

Westwood, Kansas, 66205, United States

RECRUITING

John Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

Mass General Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10043, United States

RECRUITING

Sarah Cannon Research Institute Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

University Health Network Princess Margaret Cancer Center

Toronto, Ontario, M5G 2C4, 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

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Doug Warner, MD

  Tyra Biosciences, Inc

  STUDY CHAIR

Central Study Contacts

Grace Indyk

CONTACT

858-356-2323; TyraClinicalTrials@tyra.bio

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 8, 2025
• Study Start: April 24, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

US (9); CA (1); KR (4); TW (2)