Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations (SURF301)

March 25, 2024 updated by: Tyra Biosciences, Inc

A Multicenter, Open-label Phase 1/2 Study of TYRA300 in Advanced Urothelial Carcinoma and Other Solid Tumors With Activating FGFR3 Gene Alterations (SURF301)

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

310

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Macquarie Park, New South Wales, Australia, 2109
        • Recruiting
        • Macquarie University
        • Contact:
          • Phone Number: 61-2-9812-3000
    • Queensland
      • Southport, Queensland, Australia, 4215
        • Recruiting
        • Tasman Oncology
        • Contact:
          • Phone Number: 61-7-5613-2480
      • Woolloongabba, Queensland, Australia, 4102
        • Recruiting
        • Princess Alexandra Hospital
        • Contact:
          • Phone Number: 61-7-3176-2111
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Recruiting
        • Austin Health
        • Contact:
          • Phone Number: 61-3-9496-5000
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Research Unit
        • Contact:
          • Phone Number: 61-1800-111-440
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Linear Clinical Research Limited
        • Contact:
          • Phone Number: 61-1300-546-327
  • France
      • Saint Herblain, France, 44805
        • Recruiting
        • Institut de Cancérologie de l'Ouest (ICO)
        • Contact:
          • Phone Number: 33-(0)-2-40-67-99-77
      • Toulouse, France, 31059
        • Recruiting
        • Institut Claudius Regaud, IUCT-Oncopole
        • Contact:
          • Phone Number: 33-(0)-5-31-15-58-10
      • Villejuif, France, 94805
        • Recruiting
        • Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
        • Contact:
          • Phone Number: 33-(0)-1-42-11-42-11
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Vall d'Hebron Institut d'Oncologia (VHIO)
        • Contact:
          • Phone Number: 34-93-254-34-50
      • Barcelona, Spain, 08023
        • Recruiting
        • NEXT Barcelona - Hospital Quironsalud Barcelona
        • Contact:
          • Phone Number: 34-93-238-16-61
      • Madrid, Spain, 28223
        • Recruiting
        • NEXT Madrid - Hospital Universitario Quironsalud Madrid
        • Contact:
          • Phone Number: 34-902-08-98-00
  • United States
    • Florida
      • Ocala, Florida, United States, 34474
        • Withdrawn
        • Florida Cancer Affiliates - Ocala - Main (Ocala Oncology - Ocala)
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
        • Contact:
          • Phone Number: 617-632-3000
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • UMASS Memorial Medical Center
        • Contact:
          • Phone Number: 508-334-1000
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Memorial Sloan Kettering Cancer Center (MSKCC)
        • Contact:
          • Phone Number: 212-639-2000
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke Cancer Institute (DCI) - Duke Cancer Center
        • Contact:
          • Phone Number: 919-668-4615
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic - Main Campus
        • Contact:
          • Phone Number: 216-444-2200
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Withdrawn
        • Prisma Health Cancer Institute - Faris
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
        • Contact:
          • Phone Number: 615-936-1782
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Seattle Cancer Care Alliance (SCCA) - South Lake Union
        • Contact:
          • Phone Number: 855-557-0555

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

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 Measures

Outcome Measure
Time Frame
Phase 1 Part A: To determine the maximum tolerated doses (MTD).
Time Frame: Initiation of study treatment through 28 days.
Initiation of study treatment through 28 days.
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).
Time Frame: Initiation of study treatment through 28 days (up to approximately 18 months).
Initiation of study treatment through 28 days (up to approximately 18 months).
Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.
Time Frame: Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).
Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
Time Frame: Initiation of study treatment through 28-days post treatment (up to 2 years).
Initiation of study treatment through 28-days post treatment (up to 2 years).
Frequency in changes in laboratory parameters and physical signs of toxicity.
Time Frame: Initiation of study treatment through 28-days post treatment (up to 2 years).
Initiation of study treatment through 28-days post treatment (up to 2 years).
Pharmacokinetics: maximum plasma concentration (Cmax).
Time Frame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
Time Frame: Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
Pharmacokinetics: area under the plasma concentration-time curve (AUC).
Time Frame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: half-life of TYRA-300 (t1/2).
Time Frame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
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.
Time Frame: From enrollment, every 8 or 12 weeks (up to 2 years).
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.
Time Frame: From enrollment, every 8 or 12 weeks (up to 5 years).
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.
Time Frame: From enrollment up to 5 years.
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.
Time Frame: Up to 5 years.
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.
Time Frame: 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)].
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)].

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tyra Biosciences, Inc

Investigators

  • Study Chair: Hiroomi Tada, M.D., Ph.D., Tyra Biosciences, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 22, 2022

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

September 6, 2022

First Submitted That Met QC Criteria

September 15, 2022

First Posted (Actual)

September 16, 2022

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 25, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TYR300-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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