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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

PHASE1PHASE2ACTIVE_NOT_RECRUITING

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.

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.

Eligibility criteria

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

Inclusion criteria

  1. Men and women 18 years of age or older.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
  3. Histologically confirmed advanced solid tumor who have exhausted standard therapeutic options.
  4. Evaluable (Part A) or measurable (Part B) disease according to RECIST v1.1.
  5. Histologically confirmed advanced solid tumor with an eligible FGFR3 gene mutation or fusion (Part B).
  6. Men and women 18 years of age or older.
  7. ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70.
  8. At least 1 measurable lesion by RECIST v1.1.
  9. 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.
  10. Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who has not received a prior FGFR inhibitor.
  11. Any solid tumor with an eligible FGFR3 gene mutation or rearrangement.

Exclusion criteria

  1. Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
  2. Any ocular condition likely to increase the risk of eye toxicity.
  3. History of or current uncontrolled cardiovascular disease.
  4. Active, symptomatic, or untreated brain metastases.
  5. Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300.
  6. Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1PHASE2

trial

Study ID

NCT05544552

Intervention or treatment

DRUG: TYRA-300

Conditions

  • 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

  • Condition: Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma and more

  • DRUG: TYRA-300

  • Macquarie Park, New South Wales, Australia and more

  • Sponsor: Tyra Biosciences, Inc

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Are you running this trial?

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Research sites nearby

Closest Location:

Macquarie University

Select from list below to view details:

  • Macquarie University

    Macquarie Park, New South Wales, Australia

  • Tasman Oncology

    Southport, Queensland, Australia

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, Australia

  • Austin Health

    Heidelberg, Victoria, Australia

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Who is running the clinical trial?

TBI

Tyra Biosciences, Inc

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
    EXPERIMENTAL: Phase 1 Part B - dose expansion
    • TYRA-300 taken once or twice daily by mouth in 28-day cycles.
    Drug: TYRA-300
      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

        What is the study measuring?

        Primary Outcome

        MeasureDescriptionTime 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

        MeasureDescriptionTime 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)].
        Are you running this trial?If you're a clinic or sponsor, you can claim this study.
        Claim this trial

        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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