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

NCT05544552 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TYR300-101
• Study Type: interventional
• Target: 310
• Locations: 4 countries
• Sites: 19

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.

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

Keywords

bladder; FGFR3 gene activation; FGFR3 gene alterations; FGFR3 gene fusion/rearrangement; FGFR3 gene mutation; FGFR3 gene translocation; FGFR3 positive; Fibroblast growth factor receptor 3 (FGFR3); Fibroblast growth factor receptor 3 alterations; locally advanced cancer; metastatic cancer; solid tumors; urothelial cancer; urothelial carcinoma; Urinary tract cancer; Urinary tract tumor; Urinary tract carcinoma

Outcome Measures

Primary Outcomes (3)

• Phase 1 Part A: To determine the maximum tolerated doses (MTD).

  Initiation of study treatment through 28 days.

• Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).

  Initiation of study treatment through 28 days (up to approximately 18 months).

• Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.

  Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).

Secondary Outcomes (11)

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.

  Initiation of study treatment through 28-days post treatment (up to 2 years).

• Frequency in changes in laboratory parameters and physical signs of toxicity.

  Initiation of study treatment through 28-days post treatment (up to 2 years).

• Pharmacokinetics: maximum plasma concentration (Cmax).

  Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).

• Pharmacokinetics: time to reach maximum plasma concentration (Tmax).

  Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).

• Pharmacokinetics: area under the plasma concentration-time curve (AUC).

  Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).

Study Arms (3)

Phase 1 Part A - dose escalation

EXPERIMENTAL

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

Drug: TYRA-300

Phase 1 Part B - dose expansion

EXPERIMENTAL

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

Drug: TYRA-300

Phase 2

EXPERIMENTAL

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

Drug: TYRA-300

Interventions

TYRA-300 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 A - dose escalation; Phase 1 Part B - dose expansion; Phase 2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tyra Biosciences, Inc: lead

Study Sites (19)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

UMass Memorial Medical Center

Worchester, Massachusetts, 01655, United States

Location

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10021, United States

Location

Duke Cancer Institute (DCI) - Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic - Main Campus

Cleveland, Ohio, 44195, United States

Location

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

Nashville, Tennessee, 37232, United States

Location

Seattle Cancer Care Alliance (SCCA) - South Lake Union

Seattle, Washington, 98109, United States

Location

Macquarie University

Macquarie Park, New South Wales, 2109, Australia

Location

Tasman Oncology

Southport, Queensland, 4215, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Research Unit

Melbourne, Victoria, 3000, Australia

Location

Linear Clinical Research Limited

Nedlands, Washington, 6009, Australia

Location

Institut de Cancerologie de L'Ouest (ICO)

Saint-Herblain, 44805, France

Location

Institut Claudius Regaud, IUCT-Oncopole

Toulouse, 31059, France

Location

Gustave Roussy (Institut de Cancerologie Gustave-Roussy)

Villejuif, 94805, France

Location

NEXT Barcelona - Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

Location

Vall d'Hebron Institut d'Oncologia (VHIO)

Barcelona, 08035, Spain

Location

NEXT Madrid - Hospital Universitario Quironsalud Madrid

Madrid, 28223, Spain

Location

Related Publications (1)

• Matin SF, Adibi M, Shah AY, Alhalabi O, Corn P, Guo C, Amirtharaj R, Xiao L, Lange S, Duose DY, Wang S, Pal S, Campbell MT. Phase 1b Trial Evaluating Tolerability and Activity of Targeted Fibroblast Growth Factor Receptor Inhibition in Localized Upper Tract Urothelial Carcinoma. J Urol. 2024 Jun;211(6):784-793. doi: 10.1097/JU.0000000000003928. Epub 2024 Apr 4.

  PMID: 38573872 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Urologic Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Doug Warner

  Tyra Biosciences, Inc

  STUDY CHAIR

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: September 6, 2022
• First Posted: September 16, 2022
• Study Start: November 22, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (7); AU (6); FR (3); ES (3)