Low Grade Upper Tract Urothelial Carcinoma
Conditions
Keywords
Low-grade UTUC, Upper Tract Urothelial Carcinoma, Low Grade Upper Tract Urothelial Carcinoma, FGFR Gene Amplification, FGFR Gene Alteration, FGFR Gene Alterations, FGFR3 Mutation, FGFR3 Mutations, FGFR3 Gene Fusions
Brief summary
A Phase 2A/B study of Dabogratinib (TYRA-300) in Low Grade Upper Tract Urothelial Carcinoma
Detailed description
A Phase 2A/B, Multi-center, Open-Label Study Evaluating the Efficacy and Safety of Dabogratinib (TYRA-300) in Participants with Low Grade Upper Tract Urothelial Carcinoma (SURF303)
Interventions
DRUGDabogratinib (TYRA-300) 60mg
Self-administered 60mg dose Oral tablet(s) given daily
DRUGDabogratinib (TYRA-300) 80mg
Self-administered 80mg dose Oral tablet(s) given daily
DRUGDabogratinib (TYRA-300) TBD
To be determined: 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
Two doses will be explored in Phase 2A (Dose Cohort A (DCA) 80 mg QD) and Dose Cohort B (DCB) 60 mg QD) in parallel design, enrolled by 1:1 randomization. Once the optimized dose is identified, additional participants may be enrolled at the recommended Phase 2B dose to further investigate the efficacy, safety, PK, and therapeutic activity of dabogratinib prior to the official initiation of Phase 2B enrollment. Up to 130 participants may be enrolled in Phase 2A. In Phase 2B, approximately 100 participants will be enrolled.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants ≥ 18 years of age at the time of informed consent and willing and able to comply with all required study procedures 2. Confirmed LOW RISK LG UTUC (both favorable and unfavorable) per AUA 3. At least 5mm of marker lesion left behind 4. Participants must have previous genomic report or archival/fresh tissue in addition to urine sample for retrospective genomic testing 5. Identification of marker lesion(s) within 8 weeks prior to randomization (refer to Inclusion Criterion #2) 6. If synchronous NMIBC, NMIBC must be fully resected and low-grade Ta or T1 7. No prior BCG administration within 1 year of date of consent. 8. No intravesical chemotherapy within 8 weeks prior to C1D1 (including UGN-101). 9. No systemic chemotherapy within 3 months prior to C1D1 10. ECOG 0-2 11. Pathology consists of pure urothelial carcinoma 12. Adequate bone marrow, liver, and renal function: 1. i. Absolute neutrophil count (ANC) ≥1,500/mm3 ii. Platelet count ≥75,000/mm3 iii. Hemoglobin ≥10.0 g/dL 2. i. Total bilirubin ≤ ULN ii. Alanine aminotransferase (ALT) ≤ ULN iii. Aspartate aminotransferase (AST) ≤ ULN 3. Estimated glomerular filtration rate \>60 mL/min 4. Serum Phosphate level ≤ ULN prior to starting treatment 5. International normalized ratio (INR) ≤1.5 × ULN
Exclusion criteria
1. Evidence or any features of high grade (HG) UTUC 2. History of carcinoma in situ (CIS) 3. History of prostatic urethral involvement 4. Current or previous history of muscle invasive bladder cancer 5. Current or previous history of lymph node positive and/or metastatic bladder cancer 6. Evidence of squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma or small cell of the bladder 7. Currently receiving systemic cancer therapy (cytotoxic or immunotherapy) 8. Current or prior history of pelvic external beam radiotherapy for bladder cancer 9. Current or history of receiving a prior FGFR inhibitor 10. Systemic immunotherapy within 6 months prior to randomization 11. Treatment with an investigational agent within 30 days or 5 half-lives from randomization, whichever is shorter; compounds with an unknown half-life will be default to 30 days. 12. Prior treatment with an intravesical or intracavitary agent within 8 weeks of C1D1. 13. Current evidence of central serous retinopathy or retinal pigmented epithelial detachment of any grade at time of baseline examination. 14. Requiring use of medications that are potential inhibitors or inducers of CYP3A (prohibited list of medications)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the efficacy of Dabogratinib in LG UTUC FGFR3+ participants (proportion of participants with a CR within 6 months out of all LG UTUC FGFR3+ participants) | within 6 months | Complete response (CR) rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the efficacy of Dabogratinib in LG UTUC in all participants (proportion of participants with a CR within 6 months out of all LG UTUC participants) | at 6 months | Complete Response (CR) rate |
| Duration of Response (DOR)(median time for CR duration in those participants who achieve a CR) | up to 36 months | — |
| Complete Response (proportion of participants who continue to have a CR at 12 and 24 months) | at 12 and 24 months | — |
| Safety and tolerability of dabogratinib | Up to 2 years | Incidence rate and severity of adverse events |
| Rate of renal preservation after treatment with dabogratinib | Up to 2 years | Proportion of participants who did not undergo a nephrectomy or nephroureterectomy |
| Change from unresectable UTUC to resectable UTUC | Up to 2 years | Proportion of participants with unresectable disease at baseline who convert to resectable disease on dabogratinib, as assessed by the Investigator |
Countries
France, Israel, Spain, United States
Contacts
CONTACTMegan Henry
STUDY_CHAIRDoug Warner
Tyra Biosciences, Inc
Outcome results
None listed