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

Phase 2

Recruiting

• Conditions: Low-grade NMIBC; FGFR Gene Amplification; FGFR Gene Alterations; FGFR3 Gene Alteration; FGFR3 Gene Mutation; FGFR3 Gene Fusions
• Interventions: Drug: TYRA-300 60mg; Drug: TYRA-300 50mg; Drug: TYRA-300 Dose TBD

• Registration Number: NCT06995677
• Lead Sponsor: Tyra Biosciences, Inc

Brief Summary

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

Detailed Description

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

Study Timeline

• Study First Submitted: 2025-04-25
• Study First Submitted QC: 2025-05-20
• Study First Posted: 2025-05-29
• Status Verified: 2025-06
• Study Start: 2025-06
• Last Update Submitted: 2025-06-02
• Last Update Posted: 2025-06-05
• Primary Completion: 2028-02
• Study Completion: 2028-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose Cohort A (DCA)	TYRA-300 60mg	TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer
Dose Cohort B (DCB)	TYRA-300 50mg	TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer
Possible Dose Cohort C (DCC)	TYRA-300 Dose TBD	To Be Determined- TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

Primary Outcome Measures

Name	Time	Method
To assess the efficacy of TYRA-300 in LG IR-NMIBC participants	at 3 months	Complete response (CR) rate

Secondary Outcome Measures

Name	Time	Method
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
To assess the safety and tolerability of TYRA-300 in LG IR-NMIBC participants	From initiation of treatment to 2 years	Assessed by adverse events
Duration of response (responders only)	time from initial response to confirmed recurrence of disease or death, up to 24 months

Trial Locations

Locations (1)

Urology Associates PC; 🇺🇸 Nashville, Tennessee, United States