Advanced Solid Tumor, Advanced Urothelial Carcinoma, Bladder Cancer, FGFR3 Gene Alteration, FGFR3 Gene Mutation, Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Non-muscle-invasive Bladder Cancer, Solid Tumor, Solid Tumor, Adult, Urinary Tract Cancer, Urinary Tract Carcinoma, Urinary Tract Tumor, Urothelial Carcinoma
Conditions
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
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.
Interventions
DRUGTYRA-300
TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.
Sponsors
Tyra Biosciences, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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). |
| 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). |
| 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)]. |
| 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). |
| 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). |
Countries
Australia, France, Spain, United States
Outcome results
None listed