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

Phase 2Active Not RecruitingNCT05544552

Tyra Biosciences, Inc310 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

310

Conditions

Locally Advanced Urothelial Carcinoma Metastatic Urothelial Carcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (19)

Dana Farber Cancer Institute

Boston, Massachusetts, United States

UMass Memorial Medical Center

Worchester, Massachusetts, United States

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

Duke Cancer Institute (DCI) - Duke Cancer Center

Durham, North Carolina, United States

Cleveland Clinic - Main Campus

Cleveland, Ohio, United States

Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville

Nashville, Tennessee, United States

Seattle Cancer Care Alliance (SCCA) - South Lake Union

Seattle, Washington, United States

Macquarie University

Macquarie Park, New South Wales, Australia

Tasman Oncology

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

...and 9 more locations

Outcomes

Primary Outcomes

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).

Secondary Outcomes

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)].

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

Overview

Conditions

Interventions

Eligibility

Locations (19)

Outcomes

Primary Outcomes

Secondary Outcomes