FGFR3 Gene Alteration, FGFR3 Gene Fusions, FGFR3 Gene Mutation, FGFR Gene Alterations, FGFR Gene Amplification, Low-grade NMIBC
Conditions
Keywords
FGFR3 gene alterations, FGFR3 gene mutations, FGFR3 gene fusions, FGFR3, Non-Muscle Invasive Bladder Cancer
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
Interventions
DRUGTYRA-300 60mg
Self-administered 60mg dose Oral tablet(s) given daily
DRUGTYRA-300 50mg
Self-administered 50mg dose Oral tablet(s) given daily
DRUGTYRA-300 Dose TBD
To Be Determined Dose: Self-administered Oral tablet(s) given daily
Sponsors
Tyra Biosciences, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the efficacy of TYRA-300 in LG IR-NMIBC participants | at 3 months | Complete response (CR) rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 |
Countries
Australia, Italy, Spain, United States
Contacts
CONTACTGina Risdall
STUDY_CHAIRDoug Warner, MD
Tyra Biosciences, Inc
Outcome results
None listed