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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

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

      PHASE2

    trial

    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

    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

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

    Secondary outcome

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

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