A study to investigate dabogratinib (TYRA-300) in participants with Low Grade Upper Tract Urothelial Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tyra Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-01

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Tyra Biosciences, Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Efficacy, Pharmacokinetic, Safety

Phase 2A: 1. To evaluate the efficacy of dabogratinib in participants with LG UTUC with FGFR3 altered tumors. 2. To select the recommended dose for Phase 2B.
Phase 2B: To evaluate the efficacy of dabogratinib in participants with LG UTUC with FGFR3 altered tumors.

Secondary objectives 6

1. 1. To evaluate the efficacy of dabogratinib in all participants with LG UTUC
2. 2. To evaluate the therapeutic activity of dabogratinib
3. 3. To evaluate the safety and tolerability of dabogratinib
4. 4. To characterize the PK profile of dabogratinib
5. 5. To determine rate of renal preservation after treatment with dabogratinib
6. 6. To evaluate the change from unresectable to resectable disease after treatment with dabogratinib

Conditions and MedDRA coding

Low Grade Upper Tract Urothelial Carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Participants ≥ 18 years of age at the time of informed consent and willing and able to comply with all required study procedures
2. 2. Confirmed LG UTUC.
3. 3. At least 5mm of marker lesion left behind
4. 4. Participants must have previous genomic report or archival/fresh tissue in addition to urine sample for retrospective genomic testing
5. 5. Identification of marker lesion(s) within 8 weeks prior to randomization
6. 6. If synchronous NMIBC, NMIBC must be fully resected and low-grade Ta or T1.
7. 7. No prior BCG administration within 1 year of date of consent
8. 8. No intravesical chemotherapy within 8 weeks prior to C1D1 (including UGN-101).
9. 9. No systemic chemotherapy within 3 months prior to C1D1
10. 10. ECOG 0-2
11. 11. Pathology consists of pure urothelial carcinoma
12. 12. Adequate bone marrow, liver, and renal function.

Exclusion criteria 14

1. 1. Evidence or any features of high grade (HG) UTUC
2. 2. History of carcinoma in situ (CIS)
3. 3. History of prostatic urethral involvement
4. 4. Current or previous history of muscle invasive bladder cancer
5. 5. Current or previous history of lymph node positive and/or metastatic bladder cancer
6. 6. Evidence of squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma or small cell of the bladder
7. 7. Currently receiving systemic cancer therapy (cytotoxic or immunotherapy)
8. 8. Current or prior history of pelvic external beam radiotherapy for bladder cancer
9. 9. Current or history of receiving a prior FGFR inhibitor
10. 10. Systemic immunotherapy within 6 months prior to randomization
11. 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. 12. Prior treatment with an intravesical or intracavitary agent within 8 weeks of C1D1
13. 13. Current evidence of central serous retinopathy or retinal pigmented epithelial detachment of any grade at time of baseline examination
14. 14. Requiring use of medications that are potential inhibitors or inducers of CYP3A (prohibited list of medications)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 2A: 1. Complete Response rate within 6 months. 2. Determination of the recommended dose for Phase 2B based on integrated safety, PK and efficacy data
2. Phase 2B: Complete Response rate within 6 months.

Secondary endpoints 6

1. 1. Complete Response rate within 6 months.
2. 2. Duration of Response in participants with LG UTUC with FGFR3 altered tumours; Complete Response rate in 12months and 24 months. Response rate within 6 months.
3. 3. Incidence and severity of Adverse Events
4. 4. PK parameters may include Cmax, Tmax, AUC0-last, AUCTau, AUC0-infinity, Vd/F, CL/F, and t1/2.
5. 5. Proportion of participants who did not undergo nephrectomy or nephroureterectomy
6. 6. Proportion of participants with unresectable disease at baseline who convert to resectable disease or CR on dabogratinib, as assessed by the Investigator

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tyra Biosciences Inc.

Sponsor organisation

Tyra Biosciences Inc.

Address

2656 State Street

City

Carlsbad

Postcode

92008-1626

Country

United States

Scientific contact point

Organisation

Tyra Biosciences Inc.

Contact name

Doug Warner

Public contact point

Organisation

Tyra Biosciences Inc.

Contact name

Doug Warner

Third parties 1

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications