Safety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations (SURF201)

Tyra Biosciences

Status and phase

Enrolling

Phase 1

Conditions

Solid Tumor

Locally Advanced Cholangiocarcinoma

Intrahepatic Cholangiocarcinoma

Metastatic Cholangiocarcinoma

Treatments

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

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

Study type

Interventional

Funder types

Industry

Identifiers

NCT06160752

TYR200-101

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.