Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations

NCT ID: NCT05544552

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 310 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-22
• Study Completion Date: 2027-06-30

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations, including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract and other advanced solid tumors.

Detailed Description

This is a single arm, multi-part, phase 1/2 global trial studying TYRA-300, a novel, potent fibroblast growth factor receptor (FGFR) 3-selective tyrosine kinase inhibitor, in advanced/metastatic urothelial carcinoma of the bladder and urinary tract, that contain activating gene alterations of FGFR3. Phase 1 is a dose-escalation study to evaluate the safety, tolerability, and PK of TYRA-300 to determine the optimal and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Phase 2 will evaluate the preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations, including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract and other advanced solid tumors.

Conditions

Locally Advanced Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Solid Tumor; Urothelial Carcinoma; Solid Tumor, Adult; Bladder Cancer; Non-muscle-invasive Bladder Cancer; FGFR3 Gene Mutation; FGFR3 Gene Alteration; Advanced Solid Tumor; Advanced Urothelial Carcinoma; Urinary Tract Cancer; Urinary Tract Tumor; Urinary Tract Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Part A - dose escalation

TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily.

Group Type: EXPERIMENTAL

TYRA-300

Intervention Type: DRUG

TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.

Phase 1 Part B - dose expansion

TYRA-300 taken once or twice daily by mouth in 28-day cycles.

Group Type: EXPERIMENTAL

TYRA-300

Intervention Type: DRUG

TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.

Phase 2

TYRA-300 taken once or twice daily by mouth in 28-day cycles at doses determined during Phase 1.

Group Type: EXPERIMENTAL

TYRA-300

Intervention Type: DRUG

TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.

Interventions

TYRA-300

TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Phase 1 Part A and Part B

• Men and women 18 years of age or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• Histologically confirmed advanced solid tumor who have exhausted standard therapeutic options.
• Evaluable (Part A) or measurable (Part B) disease according to RECIST v1.1.
• Histologically confirmed advanced solid tumor with an eligible FGFR3 gene mutation or fusion (Part B).

Phase 2

• Men and women 18 years of age or older.
• ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70.
• At least 1 measurable lesion by RECIST v1.1.
• Histologically confirmed locally advanced/metastatic tumor in one of the following categories:

• Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who have progressed on a prior FGFR inhibitor and presence of a resistance mutation or other kinase domain mutation.
• Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who has not received a prior FGFR inhibitor.
• Any solid tumor with an eligible FGFR3 gene mutation or rearrangement.

Exclusion Criteria

• Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
• Any ocular condition likely to increase the risk of eye toxicity.
• History of or current uncontrolled cardiovascular disease.
• Active, symptomatic, or untreated brain metastases.
• Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300.
• Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tyra Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Doug Warner

Role: STUDY_CHAIR

Tyra Biosciences, Inc

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

UMass Memorial Medical Center

Worchester, Massachusetts, United States

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

Duke Cancer Institute (DCI) - Duke Cancer Center

Durham, North Carolina, United States

Cleveland Clinic - Main Campus

Cleveland, Ohio, United States

Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville

Nashville, Tennessee, United States

Seattle Cancer Care Alliance (SCCA) - South Lake Union

Seattle, Washington, United States

Macquarie University

Macquarie Park, New South Wales, Australia

Tasman Oncology

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Austin Health

Heidelberg, Victoria, Australia

Peter MacCallum Cancer Research Unit

Melbourne, Victoria, Australia

Linear Clinical Research Limited

Nedlands, Washington, Australia

Institut de Cancerologie de L'Ouest (ICO)

Saint-Herblain, , France

Institut Claudius Regaud, IUCT-Oncopole

Toulouse, , France

Gustave Roussy (Institut de Cancerologie Gustave-Roussy)

Villejuif, , France

NEXT Barcelona - Hospital Quironsalud Barcelona

Barcelona, , Spain

Vall d'Hebron Institut d'Oncologia (VHIO)

Barcelona, , Spain

NEXT Madrid - Hospital Universitario Quironsalud Madrid

Madrid, , Spain

Countries

United States; Australia; France; Spain

Other Identifiers

TYR300-101

Identifier Type: -

Identifier Source: org_study_id