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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 (SURF301)

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ClinicalTrials.gov Identifier: NCT05544552
Recruitment Status : Recruiting
First Posted : September 16, 2022
Last Update Posted : February 23, 2023
Sponsor:
Information provided by (Responsible Party):
Tyra Biosciences, Inc

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: TYRA-300 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label Phase 1/2 Study of TYRA300 in Advanced Urothelial Carcinoma and Other Solid Tumors With Activating FGFR3 Gene Alterations (SURF301)
Actual Study Start Date : November 22, 2022
Estimated Primary Completion Date : November 2026
Estimated Study Completion Date : June 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 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 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.


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1 Part A: To determine the maximum tolerated doses (MTD). [ Time Frame: Initiation of study treatment through 28 days. ]
  2. 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). ]
  3. 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). ]

Secondary Outcome Measures :
  1. 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). ]
  2. 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). ]
  3. Pharmacokinetics: maximum plasma concentration (Cmax). [ Time Frame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days). ]
  4. Pharmacokinetics: time to reach maximum plasma concentration (Tmax). [ Time Frame: Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days). ]
  5. 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). ]
  6. Pharmacokinetics: half-life of TYRA-300 (t1/2). [ Time Frame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days). ]
  7. 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). ]
  8. 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). ]
  9. 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. ]
  10. 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. ]
  11. 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)]. ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 12 years of age or older.
  • ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70 for participants aged 12 to 17 years.
  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05544552


Contacts
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Contact: Jennifer M Davis (619)728-4805 TyraClinicalTrials@tyra.bio

Locations
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Sponsors and Collaborators
Tyra Biosciences, Inc
Investigators
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Study Chair: Hiroomi Tada, M.D., Ph.D. Tyra Biosciences, Inc
More Information
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Responsible Party: Tyra Biosciences, Inc
ClinicalTrials.gov Identifier: NCT05544552    
Other Study ID Numbers: TYR300-101
First Posted: September 16, 2022    Key Record Dates
Last Update Posted: February 23, 2023
Last Verified: February 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tyra Biosciences, Inc:
bladder
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
metastatic cancer
solid tumors
urothelial cancer
urothelial carcinoma
Urinary tract cancer
Urinary tract tumor
Urinary tract carcinoma
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Non-Muscle Invasive Bladder Neoplasms
Urologic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
 Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Urinary Bladder Diseases
Urologic Diseases
Male Urogenital Diseases