Safety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations
Purpose
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.
Conditions
- Locally Advanced Cholangiocarcinoma
- Intrahepatic Cholangiocarcinoma
- Solid Tumor
- Metastatic Cholangiocarcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 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.
Exclusion Criteria
- 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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1 Part A and Part B |
TYRA-200 taken once daily by mouth in 28-day cycles |
|
Recruiting Locations
Boston, Massachusetts 02114
Haley Ellis, MD
617-724-4000
More Details
- Status
- Recruiting
- Sponsor
- Tyra Biosciences, Inc
Detailed 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.