Evaluating TYRA-200 for advanced cholangiocarcinoma with FGFR2 gene alterations

A Multicenter, Open-label, First-in-Human Study of TYRA-200 in Advanced Intrahepatic Cholangiocarcinoma and Other Solid Tumors With Activating FGFR2 Gene Alterations (SURF-201)

This study is testing a new drug called TYRA-200 to see if it can help people with advanced cholangiocarcinoma and other tumors that have specific gene changes.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tyra Biosciences, Inc (industry)
• Locations: 4 sites (San Francisco, California and 3 other locations)
• Trial ID: NCT06160752 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and anti-tumor activity of TYRA-200, a novel FGFR inhibitor, in patients with advanced cholangiocarcinoma and other solid tumors that have activating FGFR2 gene alterations. The trial consists of two parts: Part A focuses on dose escalation to determine the maximum tolerated dose in patients with various advanced solid tumors, while Part B assesses the drug's preliminary anti-tumor activity specifically in patients with unresectable cholangiocarcinoma who have previously received FGFR inhibitors. Participants will take TYRA-200 orally once daily in 28-day cycles. The study aims to provide insights into the drug's pharmacokinetics and overall effectiveness.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced cholangiocarcinoma or other solid tumors that have FGFR2 gene mutations and have exhausted standard therapies.

Not a fit: Patients without FGFR2 gene alterations or those who have not previously received FGFR inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced cholangiocarcinoma who have limited treatment choices.

How similar studies have performed: Other studies have shown promise with FGFR inhibitors in similar patient populations, suggesting potential for success with this approach.

Eligibility criteria

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.

Where this trial is running

San Francisco, California and 3 other locations

• University of California San Francisco (UCSF) — San Francisco, California, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• The Ohio State University — Columbus, Ohio, United States (RECRUITING)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Grace Indyk

Conditions: Locally Advanced Cholangiocarcinoma, Intrahepatic Cholangiocarcinoma, Solid Tumor, Metastatic Cholangiocarcinoma, FGFR2 gene activation, FGFR2 gene alterations, FGFR2 gene fusion/rearrangement, FGFR2 gene mutation