Back to resultsSafety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations (SURF301)
Primary Purpose
Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Solid Tumor
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TYRA-300
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Urothelial Carcinoma focused on measuring 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
Eligibility Criteria
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 12 years of age or older.
- ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70 for participants aged 12 to 17 years.
- 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.
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.
Sites / Locations
- Florida Cancer Affiliates - Ocala - Main (Ocala Oncology - Ocala)Recruiting
- Dana Farber Cancer InstituteRecruiting
- Memorial Sloan Kettering Cancer Center (MSKCC)Recruiting
- Duke Cancer Institute (DCI) - Duke Cancer CenterRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - NashvilleRecruiting
- Seattle Cancer Care Alliance (SCCA) - South Lake UnionRecruiting
- Macquarie UniversityRecruiting
- Tasman OncologyRecruiting
- Princess Alexandra HospitalRecruiting
- Austin HealthRecruiting
- Peter MacCallum Cancer Research UnitRecruiting
- Linear Clinical Research LimitedRecruiting
- Institut de Cancerologie de L'Ouest (ICO)Recruiting
- Institut Claudius Regaud, IUCT-Oncopole
- Gustave Roussy (Institut de Cancerologie Gustave-Roussy)Recruiting
- NEXT Barcelona - Hospital Quironsalud BarcelonaRecruiting
- Vall d'Hebron Institut d'Oncologia (VHIO)Recruiting
- NEXT Madrid - Hospital Universitario Quironsalud MadridRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Phase 1 Part A - dose escalation
Phase 1 Part B - dose expansion
Phase 2
Arm Description
TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily.
TYRA-300 taken once daily by mouth in 28-day cycles.
TYRA-300 taken once daily by mouth in 28-day cycles at doses determined during Phase 1.
Outcomes
Primary Outcome Measures
Phase 1 Part A: To determine the maximum tolerated doses (MTD).
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).
Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.
Secondary Outcome Measures
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
Frequency in changes in laboratory parameters and physical signs of toxicity.
Pharmacokinetics: maximum plasma concentration (Cmax).
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
Pharmacokinetics: area under the plasma concentration-time curve (AUC).
Pharmacokinetics: half-life of TYRA-300 (t1/2).
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.
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.
Disease control rate is defined as the proportion of participants having a CR, PR or stable disease (SD) for >12 weeks.
Time to response is defined as time to first CR or PR that is subsequently confirmed according to RECIST v1.1.
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.
Full Information
NCT ID
NCT05544552
First Posted
September 6, 2022
Last Updated
August 7, 2023
Sponsor
Tyra Biosciences, Inc
1. Study Identification
Unique Protocol Identification Number
NCT05544552
Brief Title
Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations
Acronym
SURF301
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 22, 2022 (Actual)
Primary Completion Date
November 2026 (Anticipated)
Study Completion Date
June 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tyra Biosciences, Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Solid Tumor, Urothelial Carcinoma, Solid Tumor, Adult, Bladder Cancer, Non-muscle-invasive Bladder Cancer, FGFR3 Gene Mutation, FGFR3 Gene Alteration, Advanced Solid Tumor, Advanced Urothelial Carcinoma, Urinary Tract Cancer, Urinary Tract Tumor, Urinary Tract Carcinoma
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
310 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 Part A - dose escalation
Arm Type
Experimental
Arm Description
TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily.
Arm Title
Phase 1 Part B - dose expansion
Arm Type
Experimental
Arm Description
TYRA-300 taken once daily by mouth in 28-day cycles.
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
TYRA-300 taken once daily by mouth in 28-day cycles at doses determined during Phase 1.
Intervention Type
Drug
Intervention Name(s)
TYRA-300
Intervention Description
TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.
Primary Outcome Measure Information:
Title
Phase 1 Part A: To determine the maximum tolerated doses (MTD).
Time Frame
Initiation of study treatment through 28 days.
Title
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).
Time Frame
Initiation of study treatment through 28 days (up to approximately 18 months).
Title
Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.
Time Frame
Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).
Secondary Outcome Measure Information:
Title
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
Time Frame
Initiation of study treatment through 28-days post treatment (up to 2 years).
Title
Frequency in changes in laboratory parameters and physical signs of toxicity.
Time Frame
Initiation of study treatment through 28-days post treatment (up to 2 years).
Title
Pharmacokinetics: maximum plasma concentration (Cmax).
Time Frame
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Title
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
Time Frame
Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
Title
Pharmacokinetics: area under the plasma concentration-time curve (AUC).
Time Frame
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Title
Pharmacokinetics: half-life of TYRA-300 (t1/2).
Time Frame
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Title
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.
Time Frame
From enrollment, every 8 or 12 weeks (up to 2 years).
Title
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.
Time Frame
From enrollment, every 8 or 12 weeks (up to 5 years).
Title
Disease control rate is defined as the proportion of participants having a CR, PR or stable disease (SD) for >12 weeks.
Time Frame
From enrollment up to 5 years.
Title
Time to response is defined as time to first CR or PR that is subsequently confirmed according to RECIST v1.1.
Time Frame
Up to 5 years.
Title
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.
Time Frame
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)].
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 12 years of age or older.
ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70 for participants aged 12 to 17 years.
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.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer M Davis
Phone
(619)728-4805
Email
TyraClinicalTrials@tyra.bio
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroomi Tada, M.D., Ph.D.
Organizational Affiliation
Tyra Biosciences, Inc
Official's Role
Study Chair
Facility Information:
Facility Name
Florida Cancer Affiliates - Ocala - Main (Ocala Oncology - Ocala)
City
Ocala
State/Province
Florida
ZIP/Postal Code
34474
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
352-732-4032
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
617-632-3000
Facility Name
Memorial Sloan Kettering Cancer Center (MSKCC)
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
212-639-2000
Facility Name
Duke Cancer Institute (DCI) - Duke Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
919-668-4615
Facility Name
Prisma Health Cancer Institute - Faris
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
864-679-3900
Facility Name
Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
615-936-1782
Facility Name
Seattle Cancer Care Alliance (SCCA) - South Lake Union
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
855-557-0555
Facility Name
Macquarie University
City
Macquarie Park
State/Province
New South Wales
ZIP/Postal Code
2109
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Phone
61-2-9812-3000
Facility Name
Tasman Oncology
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Phone
61-7-5613-2480
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Phone
61-7-3176-2111
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Phone
61-3-9496-5000
Facility Name
Peter MacCallum Cancer Research Unit
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Phone
61-1800-111-440
Facility Name
Linear Clinical Research Limited
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Phone
61-1300-546-327
Facility Name
Institut de Cancerologie de L'Ouest (ICO)
City
Saint Herblain
ZIP/Postal Code
44805
Country
France
Individual Site Status
Recruiting
Facility Contact:
Phone
33-(0)-2-40-67-99-77
Facility Name
Institut Claudius Regaud, IUCT-Oncopole
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
Phone
33-(0)-5-31-15-58-10
Facility Name
Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Contact:
Phone
33-(0)-1-42-11-42-11
Facility Name
NEXT Barcelona - Hospital Quironsalud Barcelona
City
Barcelona
ZIP/Postal Code
08023
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
Phone
34-93-238-16-61
Facility Name
Vall d'Hebron Institut d'Oncologia (VHIO)
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
Phone
34-93-254-34-50
Facility Name
NEXT Madrid - Hospital Universitario Quironsalud Madrid
City
Madrid
ZIP/Postal Code
28223
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
Phone
34-902-08-98-00
12. IPD Sharing Statement
Learn more about this trial
Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations
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