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

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

Tracking Information

• First Submitted Date: September 6, 2022
• First Posted Date: September 16, 2022
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: November 22, 2022
• Estimated Primary Completion Date: November 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 15, 2022)

• Phase 1 Part A: To determine the maximum tolerated doses (MTD). [ Time Frame: 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). ]
• 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). ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 15, 2022)

• 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). ]
• 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). ]
• Pharmacokinetics: maximum plasma concentration (Cmax). [ Time Frame: 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). ]
• 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). ]
• Pharmacokinetics: half-life of TYRA-300 (t1/2). [ Time Frame: 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). ]
• 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). ]
• 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. ]
• 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. ]
• 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)]. ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations
• 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)
• 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.
• 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

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.

Study Arms

• Experimental: Phase 1 Part A - dose escalation
  TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily.
  Intervention: Drug: TYRA-300
• Experimental: Phase 1 Part B - dose expansion
  TYRA-300 taken once daily by mouth in 28-day cycles.
  Intervention: Drug: TYRA-300
• Experimental: Phase 2
  TYRA-300 taken once daily by mouth in 28-day cycles at doses determined during Phase 1.
  Intervention: Drug: TYRA-300

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 15, 2022): 310
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2027
• Estimated Primary Completion Date: November 2026 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, France, Spain, United States

Administrative Information

• NCT Number: NCT05544552
• Other Study ID Numbers: TYR300-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tyra Biosciences, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Tyra Biosciences, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Tyra Biosciences, Inc
• Verification Date: February 2023