Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma (SURF303)

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)

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

Study Overview

• Status: Recruiting
• Conditions: Low Grade Upper Tract Urothelial Carcinoma
• Intervention / Treatment: Drug: Dabogratinib (TYRA-300) 60mg; Drug: Dabogratinib (TYRA-300) 80mg; Drug: Dabogratinib (TYRA-300) TBD

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)

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Grace Indyk; Phone Number: 858-356-2323; Email: TyraClinicalTrials@tyra.bio

Study Locations

• United States
  • Illinois
    • Lisle, Illinois, United States, 60532
      • Recruiting
      • Duly Health and Care Chicago
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • Recruiting
      • First Urology
  • Ohio
    • Cleveland, Ohio, United States, 44111
      • Recruiting
      • Cleveland Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37209-4035
      • Recruiting
      • Urology Associates, P C
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Drug Dose Cohort A (DCA) 60mg; Dabogratinib (TYRA-300) monotherapy in Participants	Drug: Dabogratinib (TYRA-300) 60mg; Self-administered 60mg dose Oral tablet(s) given daily; Other Names: TYRA-300
Experimental: Study Drug Dose Cohort B (DCB) 80mg; Dabogratinib (TYRA-300) monotherapy in Participants	Drug: Dabogratinib (TYRA-300) 80mg; Self-administered 80mg dose Oral tablet(s) given daily; Other Names: TYRA-300
Experimental: Possible Study Drug Dose Cohort C (DCC) TBD mg; Dabogratinib (TYRA-300) monotherapy in Participants	Drug: Dabogratinib (TYRA-300) TBD; To be determined: Self-administered Oral tablet(s) given daily; Other Names: TYRA-300

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Complete response (CR) rate	within 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Complete Response (CR) rate	at 6 months
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	Incidence rate and severity of adverse events	Up to 2 years
Rate of renal preservation after treatment with dabogratinib	Proportion of participants who did not undergo a nephrectomy or nephroureterectomy	Up to 2 years
Change from unresectable UTUC to resectable UTUC	Proportion of participants with unresectable disease at baseline who convert to resectable disease on dabogratinib, as assessed by the Investigator	Up to 2 years

Collaborators and Investigators

• Sponsor: Tyra Biosciences, Inc
• Investigators: Study Chair: Erik T. Goluboff, MD, MBA, Tyra Biosciences, Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): November 1, 2030

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Upper Tract Urothelial Carcinoma; FGFR3 Mutations; FGFR3 Mutation; Low-grade UTUC; Low Grade Upper Tract Urothelial Carcinoma; FGFR Gene Amplification; FGFR Gene Alteration; FGFR Gene Alterations; FGFR3 Gene Fusions
• Other Study ID Numbers: TYR300-203; 2025-523539-20-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No