NCT06160752

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-200 in cancers with FGFR2 activating gene alterations, including unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
16mo left

Started Nov 2023

Typical duration for phase_1

Geographic Reach
1 country

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress65%
Nov 2023Sep 2027

Study Start

First participant enrolled

November 22, 2023

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

November 29, 2023

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 7, 2023

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2027

Last Updated

October 3, 2024

Status Verified

October 1, 2024

Enrollment Period

2.8 years

First QC Date

November 29, 2023

Last Update Submit

October 1, 2024

Conditions

Locally Advanced CholangiocarcinomaIntrahepatic CholangiocarcinomaSolid TumorMetastatic Cholangiocarcinoma

Keywords

FGFR2 gene activationFGFR2 gene alterationsFGFR2 gene fusion/rearrangementFGFR2 gene mutationFGFR2 gene translocationFGFR2Fibroblast growth factor receptor 2 (FGFR2)Fibroblast growth factor receptor 2 alterationslocally advanced cancermetastatic cancersolid tumorscholangiocarcinomaintrahepatic cholangiocarcinomaunresectable cholangiocarcinomametastatic cholangiocarcinomafibroblast growth factor receptor inhibitor

Outcome Measures

Primary Outcomes (2)

  • Phase 1 Part A: To determine the maximum tolerated dose (MTD) of TYRA-200.

    Initiation of study treatment through 28 Days

  • Phase 1 Part B: To determine the optimal dose of TYRA-200.

    Initiation of study treatment through 28 days (up to approximately 18 months

Secondary Outcomes (11)

  • Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.

    From day 1 treatment through 28-days post treatment (up to 2 years)

  • Frequency in changes in laboratory parameters and physical signs of toxicity.

    From day 1 treatment through 28-days post treatment (up to 2 years)

  • Pharmacokinetics: maximum plasma concentration (Cmax).

    From Day 1 through Cycle 3 Day 1 (each cycle is 28 days)

  • Pharmacokinetics: time to reach maximum plasma concentration (Tmax).

    From Day 1 through Cycle 3 Day 1 (each cycle is 28 days)

  • Pharmacokinetics: area under the plasma concentration-time curve (AUC).

    From Day 1 through Cycle 3 Day 1 (each cycle is 28 days)

  • +6 more secondary outcomes

Study Arms (1)

Phase 1 Part A and Part B

EXPERIMENTAL

TYRA-200 taken once daily by mouth in 28-day cycles

Drug: Phase 1 Part A - dose escalation TYRA-200 taken once daily by mouth in 28-day cyclesDrug: Phase 1 Part B - dose expansion TYRA-200 taken once daily by mouth in 28-day cycles

Interventions

Phase 1 Part A - dose escalation TYRA-200 taken once daily by mouth in 28-day cyclesDRUG

TYRA-200 is an oral, novel potent FGFR 1/2/3 tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR2.

Phase 1 Part A and Part B
Phase 1 Part B - dose expansion TYRA-200 taken once daily by mouth in 28-day cyclesDRUG

TYRA-200 is an oral, novel potent FGFR 1/2/3 tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR2.

Phase 1 Part A and Part B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Phase 1 Part A
  • Men and women 18 years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
  • Any histologically confirmed advanced solid tumor with FGFR/FGF pathway alterations including FGFR gene mutations, fusions, and amplifications, as well as gene amplifications of FGFR ligands, who have exhausted or refused approved standard therapies.
  • Evaluable disease according to RECIST v1.1.
  • Phase 1 Part B
  • Men and women 18 years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
  • Histologically confirmed locally advanced/metastatic intrahepatic cholangiocarcinoma with a previously identified FGFR2 gene mutation or rearrangement.
  • Must have received a prior FGFR inhibitor. Participants may have received more than 1 prior FGFR inhibitor.
  • Presence of an FGFR2 kinase domain mutation that confers resistance to previous/other FGFR inhibitors; resistance mutations should be identified by a US Food and Drug Administration authorized/approved companion diagnostic or a Clinical Laboratory Improvement Amendments (CLIA) validated local test performed in a certified laboratory.
  • At least 1 measurable lesion by RECIST v1.1.

You may not qualify if:

  • Discontinued a prior anti-FGFR therapy due to significant toxicity, defined as hepatotoxicity ≥Grade 3 or any Grade 4 toxicity according to CTCAE v5.0.
  • 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-200.
  • Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

University of California San Francisco (UCSF)

San Francisco, California, 94143, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

CholangiocarcinomaAcrocephalosyndactyliaNeoplasm Metastasis

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsCraniosynostosesSynostosisDysostosesBone Diseases, DevelopmentalBone DiseasesMusculoskeletal DiseasesSyndactylyCraniofacial AbnormalitiesMusculoskeletal AbnormalitiesLimb Deformities, CongenitalCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Doug Warner

    Tyra Biosciences, Inc

    STUDY CHAIR

Central Study Contacts

Grace Indyk

CONTACT

(619)728-4805TyraClinicalTrials@tyra.bio

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 29, 2023

First Posted

December 7, 2023

Study Start

November 22, 2023

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2027

Last Updated

October 3, 2024

Record last verified: 2024-10

Locations

US(4)