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.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
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.
Primary outcome measure(s)
Phase 1 Part A: To determine the maximum tolerated doses (MTD). — Initiation of study treatment through 28 days.
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD). — Initiation of study treatment through 28 days (up to approximately 18 months).
Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1. — Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).
Trial sites (19)
Facility
City
Region
Status
Dana Farber Cancer Institute
Boston
Massachusetts
UMass Memorial Medical Center
Worchester
Massachusetts
Memorial Sloan Kettering Cancer Center (MSKCC)
New York
New York
Duke Cancer Institute (DCI) - Duke Cancer Center
Durham
North Carolina
Cleveland Clinic - Main Campus
Cleveland
Ohio
Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
Nashville
Tennessee
Seattle Cancer Care Alliance (SCCA) - South Lake Union
Seattle
Washington
Macquarie University
Macquarie Park
New South Wales
Tasman Oncology
Southport
Queensland
Princess Alexandra Hospital
Woolloongabba
Queensland
Austin Health
Heidelberg
Victoria
Peter MacCallum Cancer Research Unit
Melbourne
Victoria
Linear Clinical Research Limited
Nedlands
Washington
Institut de Cancerologie de L'Ouest (ICO)
Saint-Herblain
France
Institut Claudius Regaud, IUCT-Oncopole
Toulouse
France
Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
Villejuif
France
NEXT Barcelona - Hospital Quironsalud Barcelona
Barcelona
Spain
Vall d'Hebron Institut d'Oncologia (VHIO)
Barcelona
Spain
NEXT Madrid - Hospital Universitario Quironsalud Madrid
Madrid
Spain
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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