Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

NCT06995677 | Recruiting Phase 2 FDA Drug

• 1 other identifier: TYR300-202
• Study Type: interventional
• Target: 90
• Locations: 4 countries
• Sites: 36

Brief Summary

Phase 2 Study of TYRA-300 in FGFR3 Altered Low Grade, Intermediate Risk NMIBC

Conditions

Low-grade NMIBC; FGFR Gene Amplification; FGFR3 Gene Mutation; FGFR3 Gene Fusions; FGFR Gene Alterations; FGFR3 Gene Alteration

Keywords

FGFR3 gene alterations; FGFR3 gene mutations; FGFR3 gene fusions; FGFR3; Non-Muscle Invasive Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of TYRA-300 in LG IR-NMIBC participants

  Complete response (CR) rate

  at 3 months

Secondary Outcomes (6)

• Duration of response (responders only)

  time from initial response to confirmed recurrence of disease or death, up to 24 months

• Time to recurrence (responders only)

  time from start of response to confirmed recurrence of disease, up to 24 months

• Recurrence-free survival rate (responders only)

  at 12 months and 24 months

• Progression-free survival (all participants)

  time from randomization to the progression of disease or death from any cause, whichever occurs first, up to 24 months

• Incidence and severity of adverse events

  Up to 2 years

Study Arms (3)

Dose Cohort A (DCA)

EXPERIMENTAL

TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

Drug: TYRA-300 60mg

Dose Cohort B (DCB)

EXPERIMENTAL

TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

Drug: TYRA-300 50mg

Possible Dose Cohort C (DCC)

EXPERIMENTAL

To Be Determined- TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

Drug: TYRA-300 Dose TBD

Interventions

TYRA-300 60mg DRUG

Self-administered 60mg dose Oral tablet(s) given daily

Dose Cohort A (DCA)

TYRA-300 50mg DRUG

Self-administered 50mg dose Oral tablet(s) given daily

Dose Cohort B (DCB)

TYRA-300 Dose TBD DRUG

To Be Determined Dose: Self-administered Oral tablet(s) given daily

Possible Dose Cohort C (DCC)

Eligibility Criteria

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

You may qualify if:

• Participants age 18 and over of informed consent and willing and able to comply with all requires study procedures
• Able to understand and given written informed consent
• Participants with histologically confirmed low-grade NMIBC within 6 weeks prior to randomization with prior diagnostic biopsy/TURBT to confirm stage and grade and with at least 3 mm and no more than 12 mm total (1/2 a resectoscope loop to 2 loops, refer to Section 8.1.5) residual visible tumor as a marker lesion(s) left behind:
• Ta low grade
• T1 low grade
• Participants must have intermediate risk NMIBC, defined as having any of the following characteristics (AUA Guidelines, 2024)
• Recurrence within 1 year, LG Ta
• Solitary LG Ta \>3cm
• LG Ta, multifocal
• LG T1
• Documented activating FGFR3 mutation or fusion (Appendix 4)
• No evidence of urothelial carcinoma of the upper urinary tract (confirmed by imaging) or prostatic urethra within 6 months of randomization
• No prior BCG administration within 1 year of date of consent.
• No intravesical chemotherapy within 8 weeks prior to C1D1.
• ECOG 0-1

You may not qualify if:

• Presence of tumor in ureter or prostatic urethra:
• Current or previous history of muscle invasive bladder cancer
• Current or previous history of lymph node positive and/or metastatic bladder cancer
• Evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder
• Currently receiving systemic cancer therapy (cytotoxic, immunotherapy, targeted)
• Currently receiving treatment with a prohibited therapy (refer to Section 6.7.1)
• Current or prior history of pelvic external beam radiotherapy
• Current or history of receiving a prior FGFR inhibitor
• Systemic immunotherapy within 6 months prior to randomization
• Treatment with an investigational agent within 30 days or 5 half-lives from randomization, whichever is shorter; compounds with an unknown half-life will default to the 30 days.
• Prior treatment with an intravesical agent within 8 weeks prior to C1D1
• Current ongoing toxicity from previous therapy
• Had major surgery within 4 weeks prior to C1D1
• Any reason that in the view of the investigator, would substantially impair the ability of the participant to comply with study procedures and/or risk to the participant (i.e., uncontrolled diabetes)
• Females who are pregnant, breastfeeding or planning to become pregnant within 6 months after the last dose of TYRA-300 and males who plan to father a child while enrolled in this study or within 3 months after the last dose of TYRA-300

Sponsors & Collaborators

• Tyra Biosciences, Inc: lead

Study Sites (36)

Urology Centers of Alabama

Homewood, Alabama, 35209, United States

RECRUITING

Arkansas Urology

Little Rock, Arkansas, 72211, United States

RECRUITING

Tri Valley Urology - Murrieta

Murrieta, California, 92562, United States

RECRUITING

Om Research LLC

San Diego, California, 92123, United States

RECRUITING

Associated Urological Specialists

Chicago Ridge, Illinois, 60415, United States

RECRUITING

Duly Health and Care

Lisle, Illinois, 60532, United States

RECRUITING

First Urology

Jeffersonville, Indiana, 47130, United States

RECRUITING

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, 66160, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

Atlantic Health System

Morristown, New Jersey, 07960, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center for Prostate and Urologic Cancers

New York, New York, 10065, United States

RECRUITING

The Bronx Veterans Medical Research Foundation, Inc.

The Bronx, New York, 10468, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27705, United States

RECRUITING

Associate Urologist of North Carolina

Raleigh, North Carolina, 27612, United States

RECRUITING

Oregon Urology Institute

Springfield, Ohio, 97477, United States

RECRUITING

MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

RECRUITING

Keystone Urology Specialists

Lancaster, Pennsylvania, 17604, United States

RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Lowcounty Urology Clinics, P.A.

North Charleston, South Carolina, 29406, United States

RECRUITING

Conrad Pearson-Memphis

Germantown, Tennessee, 38138, United States

RECRUITING

Urology Associates PC

Nashville, Tennessee, 37209, United States

RECRUITING

Urology Austin

Austin, Texas, 78759, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Urology San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Epworth Freemasons-Victoria Parade

Richmond, Victoria, 3121, Australia

RECRUITING

Istituti Fisioterapici Ospitalieri (IFO)

Rome, Italy, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara

Pisa, 56126, Italy

RECRUITING

ASL Napoli 2 Nord - Ospedale Santa Maria delle Grazie

Pozzuoli, 80078, Italy

RECRUITING

Centro Médico Teknon

Barcelona, Spain, 08003, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, Spain, 28040, Spain

ACTIVE NOT RECRUITING

Hospital Universitario 12 de Oc

Madrid, Spain, 28041, Spain

RECRUITING

Hospital Quirón Barcelona

Barcelona, 08908, Spain

RECRUITING

MD Anderson Cancer Center - Madrid

Madrid, 28003, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

RECRUITING

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic 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

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohort A will test a TYRA-300 dose of 60mg QD. In addition, Dose Cohort B will test, in parallel, a slightly reduced dose of TYRA-300 50 mg QD. Dose Cohort C of TYRA-300 will only open if another dose needs to be explored based on the safety and efficacy results from Cohorts A and B.

Study Record Dates

• First Submitted: April 25, 2025
• First Posted: May 29, 2025
• Study Start: June 27, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); IT (4); US (24); ES (7)