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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05544552




Registration number
NCT05544552
Ethics application status
Date submitted
6/09/2022
Date registered
16/09/2022
Date last updated
3/10/2024

Titles & IDs
Public title
Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations
Scientific 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)
Secondary ID [1] 0 0
TYR300-101
Universal Trial Number (UTN)
Trial acronym
SURF301
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Urothelial Carcinoma 0 0
Metastatic Urothelial Carcinoma 0 0
Solid Tumor 0 0
Urothelial Carcinoma 0 0
Solid Tumor, Adult 0 0
Bladder Cancer 0 0
Non-muscle-invasive Bladder Cancer 0 0
FGFR3 Gene Mutation 0 0
FGFR3 Gene Alteration 0 0
Advanced Solid Tumor 0 0
Advanced Urothelial Carcinoma 0 0
Urinary Tract Cancer 0 0
Urinary Tract Tumor 0 0
Urinary Tract Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Cancer 0 0 0 0
Bladder

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TYRA-300

Experimental: Phase 1 Part A - dose escalation - TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily.

Experimental: Phase 1 Part B - dose expansion - TYRA-300 taken once or twice daily by mouth in 28-day cycles.

Experimental: Phase 2 - TYRA-300 taken once or twice daily by mouth in 28-day cycles at doses determined during Phase 1.


Treatment: Drugs: TYRA-300
TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1 Part A: To determine the maximum tolerated doses (MTD).
Timepoint [1] 0 0
Initiation of study treatment through 28 days.
Primary outcome [2] 0 0
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).
Timepoint [2] 0 0
Initiation of study treatment through 28 days (up to approximately 18 months).
Primary outcome [3] 0 0
Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.
Timepoint [3] 0 0
Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).
Secondary outcome [1] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
Timepoint [1] 0 0
Initiation of study treatment through 28-days post treatment (up to 2 years).
Secondary outcome [2] 0 0
Frequency in changes in laboratory parameters and physical signs of toxicity.
Timepoint [2] 0 0
Initiation of study treatment through 28-days post treatment (up to 2 years).
Secondary outcome [3] 0 0
Pharmacokinetics: maximum plasma concentration (Cmax).
Timepoint [3] 0 0
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Secondary outcome [4] 0 0
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
Timepoint [4] 0 0
Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
Secondary outcome [5] 0 0
Pharmacokinetics: area under the plasma concentration-time curve (AUC).
Timepoint [5] 0 0
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Secondary outcome [6] 0 0
Pharmacokinetics: half-life of TYRA-300 (t1/2).
Timepoint [6] 0 0
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
From enrollment, every 8 or 12 weeks (up to 2 years).
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
From enrollment, every 8 or 12 weeks (up to 5 years).
Secondary outcome [9] 0 0
Disease control rate is defined as the proportion of participants having a CR, PR or stable disease (SD) for >12 weeks.
Timepoint [9] 0 0
From enrollment up to 5 years.
Secondary outcome [10] 0 0
Time to response is defined as time to first CR or PR that is subsequently confirmed according to RECIST v1.1.
Timepoint [10] 0 0
Up to 5 years.
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
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)].

Eligibility
Key inclusion criteria
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).

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (All Phases):

* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2027
Actual
Sample size
Target
310
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Macquarie University - Macquarie Park
Recruitment hospital [2] 0 0
Tasman Oncology - Southport
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Research Unit - Melbourne
Recruitment hospital [6] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
France
State/province [9] 0 0
Saint Herblain
Country [10] 0 0
France
State/province [10] 0 0
Toulouse
Country [11] 0 0
France
State/province [11] 0 0
Villejuif
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Tyra Biosciences, Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT05544552
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Doug Warner
Address 0 0
Tyra Biosciences, Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Grace Indyk
Address 0 0
Country 0 0
Phone 0 0
(619)728-4805
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05544552