A Phase 2A/B study of Dabogratinib (TYRA-300) in Low Grade Upper Tract Urothelial Carcinoma

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)

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)