Brief Title: Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: 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)

Primary Outcome 1 - Timeframe: within 6 months

CONDITION

• Low Grade Upper Tract Urothelial Carcinoma

ELIGIBILITY

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)

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Erik T. Goluboff, MD, MBA

Role: Study Chair

Affiliation: Tyra Biosciences, Inc

Overall Contact

Name: Grace Indyk

Phone: 858-356-2323

Email: [email protected]

LOCATION