Safety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations

Last updated: October 1, 2024
Sponsor: Tyra Biosciences, Inc
Overall Status: Active - Recruiting

Phase

1

Condition

Neuroblastoma

Liver Cancer

Biliary Tract Cancer

Treatment

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

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

Clinical Study ID

NCT06160752
TYR200-101
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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 alterationsincluding FGFR gene mutations, fusions, and amplifications, as well as geneamplifications of FGFR ligands, who have exhausted or refused approved standardtherapies.

  • 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 cholangiocarcinomawith 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 toprevious/other FGFR inhibitors; resistance mutations should be identified by a USFood and Drug Administration authorized/approved companion diagnostic or a ClinicalLaboratory Improvement Amendments (CLIA) validated local test performed in acertified laboratory.

  • At least 1 measurable lesion by RECIST v1.1.

Exclusion

Exclusion Criteria:

  • Discontinued a prior anti-FGFR therapy due to significant toxicity, defined ashepatotoxicity ≥Grade 3 or any Grade 4 toxicity according to CTCAE v5.0.

  • Has a serum phosphorus level > upper limit of normal (ULN) during screening thatremains >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 ofTYRA-200.

  • Females who are pregnant, breastfeeding, or planning to become pregnant and maleswho plan to father a child while enrolled in this study.

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: Phase 1 Part A - dose escalation TYRA-200 taken once daily by mouth in 28-day cycles
Phase: 1
Study Start date:
November 22, 2023
Estimated Completion Date:
September 30, 2027

Study Description

This is a single arm, multi-part, phase 1 clinical trial studying TYRA-200, a novel, potent fibroblast growth factor receptor (FGFR) 1/2/3 tyrosine kinase inhibitor, in unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2. Part A is a dose escalation study in participants with any advanced solid tumor with FGFR/FGF pathway alterations who have exhausted approved standard therapies. Part A will evaluate the safety, tolerability, and PK of TYRA-200 to determine the optimal and maximum tolerated dose (MTD). Part B will evaluate the preliminary antitumor activity of TYRA-200 in participants with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma who have previously received an FGFR inhibitor and have FGFR2 kinase-domain mutations resistant to other FGFR inhibitors.

Connect with a study center

  • University of California San Francisco (UCSF)

    San Francisco, California 94143
    United States

    Active - Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • The Ohio State University

    Columbus, Ohio 43210
    United States

    Active - Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

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