Locally Advanced Urothelial CarcinomaPhase 1/2SURF301NCT05544552
Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations
A Phase 1/2 study testing TYRA-300 in people with Locally Advanced Urothelial Carcinoma and Metastatic Urothelial Carcinoma, run by Tyra Biosciences, Inc at 19 sites in 4 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations, including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract and other advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Solid Tumor
- What is being tested?
- TYRA-300
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 310 participants
- Where
- 19 sitesin 4 countries
- Study dates
- 22 Nov 2022to Jun 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase 1 Part A and Part B
- Men and women 18 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- Histologically confirmed advanced solid tumor who have exhausted standard therapeutic options.
- Evaluable (Part A) or measurable (Part B) disease according to RECIST v1.1.
- Histologically confirmed advanced solid tumor with an eligible FGFR3 gene mutation or fusion (Part B).
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- Phase 2
- Men and women 18 years of age or older.
- ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70.
- At least 1 measurable lesion by RECIST v1.1.
- Histologically confirmed locally advanced/metastatic tumor in one of the following categories:
- Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who have progressed on a prior FGFR inhibitor and presence of a resistance mutation or other kinase domain mutation.
- Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who has not received a prior FGFR inhibitor.
- Any solid tumor with an eligible FGFR3 gene mutation or rearrangement.
Who cannot join
- Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
- Any ocular condition likely to increase the risk of eye toxicity.
- History of or current uncontrolled cardiovascular disease.
- Active, symptomatic, or untreated brain metastases.
- Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300.
- Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.
Trial locations and contacts
19 sites in 4 countries.
19 sites in 4 countries
United States7 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Cleveland Clinic - Main Campus
Cleveland, Ohio, 44195
Duke Cancer Institute (DCI) - Duke Cancer Center
Durham, North Carolina, 27710
Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center (MSKCC)
New York, New York, 10021
Seattle Cancer Care Alliance (SCCA) - South Lake Union
Seattle, Washington, 98109
UMass Memorial Medical Center
Worchester, Massachusetts, 01655
Australia6 sites
Austin Health
Heidelberg, Victoria, 3084
Macquarie University
Macquarie Park, New South Wales, 2109
Peter MacCallum Cancer Research Unit
Melbourne, Victoria, 3000
Linear Clinical Research Limited
Nedlands, Washington, 6009
Tasman Oncology
Southport, Queensland, 4215
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
France3 sites
Institut de Cancerologie de L'Ouest (ICO)
Saint-Herblain, 44805
Institut Claudius Regaud, IUCT-Oncopole
Toulouse, 31059
Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
Villejuif, 94805
Spain3 sites
NEXT Barcelona - Hospital Quironsalud Barcelona
Barcelona, 08023
Vall d'Hebron Institut d'Oncologia (VHIO)
Barcelona, 08035
NEXT Madrid - Hospital Universitario Quironsalud Madrid
Madrid, 28223
About this study
Official title: A Multicenter, Open-label Phase 1/2 Study of TYRA300 in Advanced Urothelial Carcinoma and Other Solid Tumors With Activating FGFR3 Gene Alterations (SURF301)
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations, including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract and other advanced solid tumors.
Read the detailed description
This is a single arm, multi-part, phase 1/2 global trial studying TYRA-300, a novel, potent fibroblast growth factor receptor (FGFR) 3-selective tyrosine kinase inhibitor, in advanced/metastatic urothelial carcinoma of the bladder and urinary tract, that contain activating gene alterations of FGFR3. Phase 1 is a dose-escalation study to evaluate the safety, tolerability, and PK of TYRA-300 to determine the optimal and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Phase 2 will evaluate the preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations, including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract and other advanced solid tumors.
- Conditions
- Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Solid Tumor, Urothelial Carcinoma, Solid Tumor, Adult, Bladder Cancer
- Being tested
- TYRA-300
- Keywords
- bladder, FGFR3 gene activation, FGFR3 gene alterations, FGFR3 gene fusion/rearrangement, FGFR3 gene mutation, FGFR3 gene translocation, FGFR3 positive, Fibroblast growth factor receptor 3 (FGFR3), Fibroblast growth factor receptor 3 alterations, locally advanced cancer, metastatic cancer, solid tumors, urothelial cancer, urothelial carcinoma, Urinary tract cancer, Urinary tract tumor, Urinary tract carcinoma
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms, Urologic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TYRA-300Drug
TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Part A - dose escalation | Experimental | TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily. Receives: Drug: TYRA-300 |
| Phase 1 Part B - dose expansion | Experimental | TYRA-300 taken once or twice daily by mouth in 28-day cycles. Receives: Drug: TYRA-300 |
| Phase 2 | Experimental | TYRA-300 taken once or twice daily by mouth in 28-day cycles at doses determined during Phase 1. Receives: Drug: TYRA-300 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 Part A: To determine the maximum tolerated doses (MTD).
Measured: Initiation of study treatment through 28 days.
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).
Measured: Initiation of study treatment through 28 days (up to approximately 18 months).
Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.
Measured: Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).
Secondary outcomes (11)
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
Measured: Initiation of study treatment through 28-days post treatment (up to 2 years).
Frequency in changes in laboratory parameters and physical signs of toxicity.
Measured: Initiation of study treatment through 28-days post treatment (up to 2 years).
Pharmacokinetics: maximum plasma concentration (Cmax).
Measured: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
Measured: Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
Pharmacokinetics: area under the plasma concentration-time curve (AUC).
Measured: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: half-life of TYRA-300 (t1/2).
Measured: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) as determined by the investigator using RECIST V1.1.
Measured: From enrollment, every 8 or 12 weeks (up to 2 years).
Duration of response will be defined as the time from the initial CR or PR to the time of relapse or death, whichever occurs first among participant with an objective response.
Measured: From enrollment, every 8 or 12 weeks (up to 5 years).
Disease control rate is defined as the proportion of participants having a CR, PR or stable disease (SD) for >12 weeks.
Measured: From enrollment up to 5 years.
Time to response is defined as time to first CR or PR that is subsequently confirmed according to RECIST v1.1.
Measured: Up to 5 years.
Progression-free survival is defined as the time from the date of first study drug administration to the earliest date of documented disease progression or death.
Measured: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (up to 5 years)].
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2022
- Study start22 Nov 2022
- Primary completionNov 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Urothelial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 310 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tyra Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Doug Warner, Study chair, Tyra Biosciences, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05544552
- Sponsor's protocol ID
- TYR300-101
- Acronym
- SURF301
- Status last verified
- Jan 2026
- First submitted
- 6 Sep 2022
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Matin SF, Adibi M, Shah AY, Alhalabi O, Corn P, Guo C, Amirtharaj R, Xiao L, Lange S, Duose DY, Wang S, Pal S, Campbell MT. Phase 1b Trial Evaluating Tolerability and Activity of Targeted Fibroblast Growth Factor Receptor Inhibition in Localized Upper Tract Urothelial Carcinoma. J Urol. 2024 Jun;211(6):784-793. doi: 10.1097/JU.0000000000003928. Epub 2024 Apr 4.
PubMed 38573872