Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer
Purpose
Phase 2 Study of TYRA-300 in FGFR3 Altered Low Grade, Intermediate Risk NMIBC
Conditions
- Low-grade NMIBC
- FGFR Gene Amplification
- FGFR Gene Alterations
- FGFR3 Gene Alteration
- FGFR3 Gene Mutation
- FGFR3 Gene Fusions
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- 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 Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Dose Cohort A (DCA) |
TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer |
|
|
Experimental Dose Cohort B (DCB) |
TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer |
|
|
Experimental 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 |
|
Recruiting Locations
Urology Associates PC
Nashville, Tennessee 37209
Nashville, Tennessee 37209
More Details
- NCT ID
- NCT06995677
- Status
- Recruiting
- Sponsor
- Tyra Biosciences, Inc
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