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

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: Active, not recruiting
• Conditions: Solid Tumor; Bladder Cancer; Advanced Solid Tumor; Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Solid Tumor, Adult; FGFR3 Gene Mutation; Urinary Tract Cancer; Locally Advanced Urothelial Carcinoma; Advanced Urothelial Carcinoma; Non-muscle-invasive Bladder Cancer; FGFR3 Gene Alteration; Urinary Tract Tumor; Urinary Tract Carcinoma
• Intervention / Treatment: Drug: TYRA-300

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

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Tasman Oncology
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Research Unit
  • Washington
    • Nedlands, Washington, Australia, 6009
      • Linear Clinical Research Limited
• France
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest (ICO)
  • Toulouse, France, 31059
    • Institut Claudius Regaud, IUCT-Oncopole
  • Villejuif, France, 94805
    • Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institut d'Oncologia (VHIO)
  • Barcelona, Spain, 08023
    • NEXT Barcelona - Hospital Quironsalud Barcelona
  • Madrid, Spain, 28223
    • NEXT Madrid - Hospital Universitario Quironsalud Madrid
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Worchester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center (MSKCC)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute (Dci) - Duke Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Main Campus
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance (SCCA) - South Lake Union

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

3

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).	Initiation of study treatment through 28 days.
Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).	Initiation of study treatment through 28 days (up to approximately 18 months).
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 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.	Initiation of study treatment through 28-days post treatment (up to 2 years).
Frequency in changes in laboratory parameters and physical signs of toxicity.	Initiation of study treatment through 28-days post treatment (up to 2 years).
Pharmacokinetics: maximum plasma concentration (Cmax).	Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).	Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
Pharmacokinetics: area under the plasma concentration-time curve (AUC).	Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
Pharmacokinetics: half-life of TYRA-300 (t1/2).	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.	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.	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.	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.	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.	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

• Sponsor: Tyra Biosciences, Inc
• Investigators: Study Chair: Doug Warner, Tyra Biosciences, Inc

Study record dates

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 (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: metastatic cancer; solid tumors; urothelial cancer; bladder; urothelial carcinoma; FGFR3 gene activation; FGFR3 gene alterations; FGFR3 gene fusion/rearrangement; FGFR3 gene mutation; FGFR3 gene translocation; FGFR3 positive; Fibroblast growth factor receptor 3 (FGFR3); Fibroblast growth factor receptor 3 alterations; locally advanced cancer; Urinary tract cancer; Urinary tract tumor; Urinary tract carcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Carcinoma; Urinary Bladder Diseases; Pathological Conditions, Signs and Symptoms; Non-Muscle Invasive Bladder Neoplasms; Neoplasm Metastasis; Urinary Bladder Neoplasms; Urologic Neoplasms; Carcinoma, Transitional Cell
• 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