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Active, not recruitingNCT05544552SURF301Updated Jan 12, 2026

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

A Phase 1/2 interventional study of TYRA-300 in Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma and Solid Tumor, sponsored by Tyra Biosciences, Inc. Active, not recruiting at 19 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-12.

Sponsored by Tyra Biosciences, Inc · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
310
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

Exclusion Criteria (All Phases):

  • 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.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
310 participants (estimated)

Study arms

  • Experimental
    Phase 1 Part A - dose escalation

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

    Drug: TYRA-300

  • Experimental
    Phase 1 Part B - dose expansion

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

    Drug: TYRA-300

  • Experimental
    Phase 2

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

    Drug: TYRA-300

Interventions

  • DrugTYRA-300

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

05

What researchers measure

Primary outcomes

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

    Time frame: Initiation of study treatment through 28 days.

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

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

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

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

Secondary outcomes

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

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

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

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

  3. Pharmacokinetics: maximum plasma concentration (Cmax).

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

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

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

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

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

  6. Pharmacokinetics: half-life of TYRA-300 (t1/2).

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

  7. ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) as determined by the investigator using RECIST V1.1.

    Time frame: From enrollment, every 8 or 12 weeks (up to 2 years).

  8. Duration of response will be defined as the time from the initial CR or PR to the time of relapse or death, whichever occurs first among participant with an objective response.

    Time frame: From enrollment, every 8 or 12 weeks (up to 5 years).

  9. Disease control rate is defined as the proportion of participants having a CR, PR or stable disease (SD) for >12 weeks.

    Time frame: From enrollment up to 5 years.

  10. Time to response is defined as time to first CR or PR that is subsequently confirmed according to RECIST v1.1.

    Time frame: Up to 5 years.

  11. Progression-free survival is defined as the time from the date of first study drug administration to the earliest date of documented disease progression or death.

    Time frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (up to 5 years)].

06

Study locations

19 sites
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • UMass Memorial Medical Center
    Worchester, Massachusetts 01655, United States
  • Memorial Sloan Kettering Cancer Center (MSKCC)
    New York, New York 10021, United States
  • Duke Cancer Institute (DCI) - Duke Cancer Center
    Durham, North Carolina 27710, United States
  • Cleveland Clinic - Main Campus
    Cleveland, Ohio 44195, United States
  • Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
    Nashville, Tennessee 37232, United States
  • Seattle Cancer Care Alliance (SCCA) - South Lake Union
    Seattle, Washington 98109, United States
  • Macquarie University
    Macquarie Park, New South Wales 2109, Australia
  • Tasman Oncology
    Southport, Queensland 4215, Australia
  • Princess Alexandra Hospital
    Woolloongabba, Queensland 4102, Australia
  • Austin Health
    Heidelberg, Victoria 3084, Australia
  • Peter MacCallum Cancer Research Unit
    Melbourne, Victoria 3000, Australia
  • Linear Clinical Research Limited
    Nedlands, Washington 6009, Australia
  • Institut de Cancerologie de L'Ouest (ICO)
    Saint-Herblain, 44805, France
  • Institut Claudius Regaud, IUCT-Oncopole
    Toulouse, 31059, France
  • Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
    Villejuif, 94805, France
  • NEXT Barcelona - Hospital Quironsalud Barcelona
    Barcelona, 08023, Spain
  • Vall d'Hebron Institut d'Oncologia (VHIO)
    Barcelona, 08035, Spain
  • NEXT Madrid - Hospital Universitario Quironsalud Madrid
    Madrid, 28223, Spain
07

References and documents

Publications

  • 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. PubMed 38573872 ↗
08

Registry details

Key details

Study ID
NCT05544552
Lead sponsor
Tyra Biosciences, Inc
Responsible party
Sponsor
First posted
Sep 16, 2022
Start date
Nov 22, 2022
Primary completion
Nov 2026 (estimated)
Completion
Jun 2027 (estimated)
Last update
Jan 12, 2026

Study contacts

Doug Warner
study chair · Tyra Biosciences, Inc

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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