Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations

Bladder Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05544552
• Other study ID #: TYR300-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 22, 2022
• Est. completion date: June 2027

Study information

• Verified date: March 2024
• Source: Tyra Biosciences, Inc
• Contact: Jennifer M Davis
• Phone: (619)728-4805
• Email: TyraClinicalTrials[@]tyra.bio
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 310
• Est. completion date: June 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Advanced Urothelial Carcinoma
• Bladder Cancer
• Carcinoma
• Carcinoma, Transitional Cell
• FGFR3 Gene Mutation
• Locally Advanced Urothelial Carcinoma
• Metastatic Urothelial Carcinoma
• Neoplasms
• Non-muscle-invasive Bladder Cancer
• Solid Tumor
• Solid Tumor, Adult
• Urinary Bladder Neoplasms
• Urinary Tract Cancer
• Urologic Neoplasms
• Urothelial Carcinoma

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Australia	Austin Health	Heidelberg	Victoria
Australia	Macquarie University	Macquarie Park	New South Wales
Australia	Peter MacCallum Cancer Research Unit	Melbourne	Victoria
Australia	Linear Clinical Research Limited	Nedlands	Western Australia
Australia	Tasman Oncology	Southport	Queensland
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
France	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
Spain	NEXT Barcelona - Hospital Quironsalud Barcelona	Barcelona
Spain	Vall d'Hebron Institut d'Oncologia (VHIO)	Barcelona
Spain	NEXT Madrid - Hospital Universitario Quironsalud Madrid	Madrid
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Cleveland Clinic - Main Campus	Cleveland	Ohio
United States	Duke Cancer Institute (DCI) - Duke Cancer Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center (MSKCC)	New York	New York
United States	Florida Cancer Affiliates - Ocala - Main (Ocala Oncology - Ocala)	Ocala	Florida
United States	Seattle Cancer Care Alliance (SCCA) - South Lake Union	Seattle	Washington
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Tyra Biosciences, Inc

Countries where clinical trial is conducted

United States,  Australia,  France,  Spain, 

Outcome

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