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

NCT ID: NCT06995677

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-27

Study Completion Date

2028-09-30

Brief Summary

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

Detailed Description

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A Phase 2 Multicenter, Open-Label Study Evaluating the Efficacy and Safety of TYRA-300 in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

Conditions

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

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Cohort A (DCA)

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

Group Type EXPERIMENTAL

TYRA-300 60mg

Intervention Type DRUG

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

Dose Cohort B (DCB)

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

Group Type EXPERIMENTAL

TYRA-300 50mg

Intervention Type DRUG

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

Possible Dose Cohort C (DCC)

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

Group Type EXPERIMENTAL

TYRA-300 Dose TBD

Intervention Type DRUG

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

Interventions

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TYRA-300 60mg

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

Intervention Type DRUG

TYRA-300 50mg

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

Intervention Type DRUG

TYRA-300 Dose TBD

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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:

1. Ta low grade
2. T1 low grade
* Participants must have intermediate risk NMIBC, defined as having any of the following characteristics (AUA Guidelines, 2024)

1. Recurrence within 1 year, LG Ta
2. Solitary LG Ta \>3cm
3. LG Ta, multifocal
4. LG T1
* Documented activating FGFR3 mutation or fusion (Appendix 4)
* Have undergone bladder mapping and identification of visible marker lesion(s) within 6 weeks prior to randomization (refer to Inclusion Criterion #3)
* 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
* Pathology consistent with pure urothelial carcinoma; if mixed histology, ensure that at least 80% of the sample is urothelial
* Adequate bone marrow, liver, and renal function:

b. Bone marrow function: i. Absolute neutrophil count (ANC) \> or = 1,500/mm3 ii. Platelet count \> or = 75,000/mm3 iii. /hemoglobin \> or = 10.0 g/dL e. Liver function: i.Total bilirubin \< or = ULN ii. Alanine aminotransferase (ALT) \< or = ULN iii. Aspartate aminotransferase (AST) \< or = ULN f. Renal function: i. estimated glomerular filtration rate \>60 mL/min calculated using the modification of diet in renal disease equation or CKD-EPI formula ii. Serum Phosphate level \< or = ULN prior to starting treatment g. Coagulation i. International normalized ratio (INR) \< or = 1.5 x ULN
* Ability to swallow tablets
* Participants (male and female) of child-bearing potential (including females who are post-menopausal for less than 1 year) must be willing to practice effective contraception while on treatment and be willing and able to continue contraception for 3 months (males) and 6 months (females) after the last dose of study treatment. Potential male participants should consider the potential impact of TYRA-300 on their ability to father a child and discuss options with the site study staff.
* Potential participants who are positive for human immunodeficiency virus (HIV) must have a viral load below the limits of detection and on stable antiretroviral therapy for at least 3 months prior to C1D1. NOTE: some of the compounds in antiretroviral therapy may be on the prohibited medications list. Allowances will be made to ensure the participant's HIV treatment continues uninterrupted following a discussion with the Sponsor's medical monitor. A discussion of the impact of the antiretroviral therapy on TYRA- 300 needs to be discussed with the potential participant prior to C1D1.
* Potential participants with chronic hepatitis B virus (HBV) infection with active disease should be on a suppressive antiviral therapy prior to C1D1.
* Potential participants patients with a history of hepatitis C virus (HCV) infection should have completed curative antiviral treatment and must have a HCV viral load below the limit of quantification.
* Potential participants with a history of HCV infection and on current treatment must have a HCV viral load below the limit of quantification

Exclusion Criteria

* 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
* Has impaired wound healing capacity
* Serum phosphate levels above the upper limit of normal during screening
* Any ocular condition likely to increase the risk of eye toxicity
* Current evidence of central serous retinopathy or retinal pigmented epithelial detachment of any grade at time of baseline examination.
* History of or current uncontrolled cardiovascular disease
* Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300
* Known history of HIV infection, or active hepatitis B or C
* History of a second primary malignancy within 3 years of signing ICF, except for nonmelanoma skin cancer and cured and active surveillance malignancies (i.e., prostate, breast) .
* Known allergy to TYRA-300 or any excipients of the formulated product
* Participants taking strong inhibitors and/or inducers of CYP3A4 enzyme
* History of prolonged QT syndrome or baseline heart rate-corrected QT interval using Fridericia formula (QTcF) interval \>470 ms
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tyra Biosciences, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Doug Warner, MD

Role: STUDY_CHAIR

Tyra Biosciences, Inc

Locations

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Tri Valley Urology - Murrieta

Murrieta, California, United States

Site Status RECRUITING

Genesis Research

San Diego, California, United States

Site Status RECRUITING

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, United States

Site Status RECRUITING

The Bronx Veterans Medical Research Foundation, Inc.

The Bronx, New York, United States

Site Status RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status RECRUITING

Urology Associates PC

Nashville, Tennessee, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

Istituti Fisioterapici Ospitalieri (IFO)

Rome, Italy, Italy

Site Status RECRUITING

Centro Médico Teknon

Barcelona, Spain, Spain

Site Status RECRUITING

Hospital Clínico San Carlos

Madrid, Spain, Spain

Site Status RECRUITING

Hospital Universitario 12 de Oc

Madrid, Spain, Spain

Site Status RECRUITING

Countries

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United States Italy Spain

Central Contacts

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Grace Indyk

Role: CONTACT

Phone: 858-356-2323

Email: [email protected]

Other Identifiers

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TYR300-202

Identifier Type: -

Identifier Source: org_study_id