Clinical trial NCT05544552: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Keywords: 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
Lead sponsor: Tyra Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2022-09-16
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Phase 1 Part A: To determine the maximum tolerated doses (MTD).
timeFrame: Initiation of study treatment through 28 days.
measure: Phase 1 Part B: To determine the recommended Phase 2 dose (R2PD).
timeFrame: Initiation of study treatment through 28 days (up to approximately 18 months).
measure: Phase 2: Overall Response Rate (ORR), defined by RECIST v1.1.
timeFrame: Initiation of study treatment until disease progression, death, unacceptable toxicity, or withdrawal (up to 2 years).
Secondary outcomes:
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
timeFrame: Initiation of study treatment through 28-days post treatment (up to 2 years).
measure: Frequency in changes in laboratory parameters and physical signs of toxicity.
timeFrame: Initiation of study treatment through 28-days post treatment (up to 2 years).
measure: Pharmacokinetics: maximum plasma concentration (Cmax).
timeFrame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
measure: Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
timeFrame: Initiation of study treatment through Cycle 3 Day 1(each cycle is 28 days).
measure: Pharmacokinetics: area under the plasma concentration-time curve (AUC).
timeFrame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
measure: Pharmacokinetics: half-life of TYRA-300 (t1/2).
timeFrame: Initiation of study treatment through Cycle 3 Day 1 (each cycle is 28 days).
measure: 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.
timeFrame: From enrollment, every 8 or 12 weeks (up to 2 years).
measure: 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.
timeFrame: From enrollment, every 8 or 12 weeks (up to 5 years).
measure: Disease control rate is defined as the proportion of participants having a CR, PR or stable disease (SD) for >12 weeks.
timeFrame: From enrollment up to 5 years.
measure: Time to response is defined as time to first CR or PR that is subsequently confirmed according to RECIST v1.1.
timeFrame: Up to 5 years.
measure: 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.
timeFrame: 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)].
Other outcomes:
Locations:
city: Ocala
country: United States
facility: Florida Cancer Affiliates - Ocala - Main (Ocala Oncology - Ocala)
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (MSKCC)
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute (DCI) - Duke Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Main Campus
state: Ohio
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance (SCCA) - South Lake Union
state: Washington
city: Macquarie Park
country: Australia
facility: Macquarie University
state: New South Wales
city: Southport
country: Australia
facility: Tasman Oncology
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Research Unit
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
state: Western Australia
city: Saint Herblain
country: France
facility: Institut de Cancerologie de L'Ouest (ICO)
city: Toulouse
country: France
facility: Institut Claudius Regaud, IUCT-Oncopole
city: Villejuif
country: France
facility: Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
city: Barcelona
country: Spain
facility: NEXT Barcelona - Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Vall d'Hebron Institut d'Oncologia (VHIO)
city: Madrid
country: Spain
facility: NEXT Madrid - Hospital Universitario Quironsalud Madrid
Study officials:
affiliation: Tyra Biosciences, Inc
name: Doug Warner
role: STUDY_CHAIR
References: