Dabogratinib treatment for 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)

This trial tests whether the oral drug dabogratinib can shrink or control low-grade upper tract urothelial carcinoma in adults who can provide tissue or urine for genomic testing.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 230 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tyra Biosciences, Inc (industry)
• Drugs / interventions: chemotherapy, immunotherapy, Dabogratinib
• Locations: 5 sites (Lisle, Illinois and 4 other locations)
• Trial ID: NCT07265947 on ClinicalTrials.gov

What this trial studies

This is a Phase 2A/B, multi-center, open-label trial giving oral dabogratinib at planned dose levels to adults with low-grade upper tract urothelial carcinoma who have a measurable marker lesion. Participants must have tissue or urine available for genomic testing and a marker lesion of at least 5 mm left in place before treatment. The study follows patients for tumor response and safety outcomes across dose cohorts (including 60 mg and 80 mg arms and an additional dose to be determined). Key eligibility includes confirmed low-risk low-grade UTUC, ECOG 0-2, and adequate organ function.

Who should consider this trial

Good fit: Adults (≥18) with confirmed low-risk low-grade upper tract urothelial carcinoma who have a measurable marker lesion and available archival/fresh tissue or urine for genomic testing are the intended participants.

Not a fit: Patients without sufficient tissue/urine for genomic testing, with high-risk disease features, or with contraindications to the drug or inadequate organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, dabogratinib could shrink or control tumors and offer a less invasive treatment option for some patients with low-grade upper tract urothelial carcinoma.

How similar studies have performed: Targeted FGFR therapies have shown activity in FGFR-altered urothelial carcinoma in advanced disease, but using dabogratinib specifically in low-grade upper tract disease is a newer application.

Eligibility 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)

Where this trial is running

Lisle, Illinois and 4 other locations

• Duly Health and Care Chicago — Lisle, Illinois, United States (RECRUITING)
• First Urology — Jeffersonville, Indiana, United States (RECRUITING)
• Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)
• Urology Associates, P C — Nashville, Tennessee, United States (RECRUITING)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Grace Indyk

Conditions: Low Grade Upper Tract Urothelial Carcinoma, Low-grade UTUC, Upper Tract Urothelial Carcinoma, FGFR Gene Amplification, FGFR Gene Alteration, FGFR Gene Alterations, FGFR3 Mutation, FGFR3 Mutations