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

PHASE1PHASE2RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

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).

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

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.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-11-22

Primary completion: 2026-11-01

Study completion finish: 2027-06-01

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT05544552

Intervention or treatment

DRUG: TYRA-300

Conditions

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

Condition: Solid Tumor, Urothelial Carcinoma and more
DRUG: TYRA-300
Macquarie Park, New South Wales, Australia and more
Sponsor: Tyra Biosciences, Inc

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Find a site

Closest Location:

Macquarie University

Research sites nearby

Select from list below to view details:

Macquarie University
Macquarie Park, New South Wales, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Austin Health
Heidelberg, Victoria, Australia
Linear Clinical Research Limited
Nedlands, Western Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1 Part A - dose escalation TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily.	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.
EXPERIMENTAL: Phase 1 Part B - dose expansion TYRA-300 taken once or twice daily by mouth in 28-day cycles.	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.
EXPERIMENTAL: Phase 2 TYRA-300 taken once or twice daily by mouth in 28-day cycles at doses determined during Phase 1.	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.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Phase 1 Part A: To determine the maximum tolerated doses (MTD).	Not Specified	Initiation of study treatment through 28 days.
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).	Not Specified	Initiation of study treatment through 28 days (up to approximately 18 months).
Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.	Not Specified	Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.	Not Specified	Initiation of study treatment through 28-days post treatment (up to 2 years).
Frequency in changes in laboratory parameters and physical signs of toxicity.	Not Specified	Initiation of study treatment through 28-days post treatment (up to 2 years).
Pharmacokinetics: maximum plasma concentration (Cmax).	Not Specified	Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).	Not Specified	Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
Pharmacokinetics: area under the plasma concentration-time curve (AUC).	Not Specified	Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: half-life of TYRA-300 (t1/2).	Not Specified	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.	Not Specified	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.	Not Specified	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.	Not Specified	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.	Not Specified	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.	Not Specified	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)].

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References

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