TYRA-200 for Bile Duct Cancer

(SURF201 Trial)

Recruiting at 3 trial locations

Overseen By Grace Indyk

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tyra Biosciences, Inc

Must be taking: Fgfr inhibitors

Disqualifiers: Cardiovascular disease, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, TYRA-200, to determine its safety and effectiveness for individuals with certain advanced cancers, such as bile duct cancer, that involve a specific gene change called FGFR2. The trial examines the drug's efficacy, its movement through the body, and any side effects. Suitable candidates have bile duct cancer that cannot be surgically removed, have tried other treatments without success, and possess a specific FGFR2 gene change that rendered previous treatments ineffective. Participants will take TYRA-200 orally once a day in 28-day cycles. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants must have received a prior FGFR inhibitor, so you may need to continue with certain treatments.

Is there any evidence suggesting that TYRA-200 is likely to be safe for humans?

Research shows that TYRA-200, a new treatment for bile duct cancer, remains in the early testing stages. Limited information exists about its safety for people. Current studies focus on determining the right dose and identifying any side effects. These studies aim to ensure the treatment's safety for patients. In this Phase 1 trial, researchers primarily assess patient reactions and potential side effects. As research progresses, more detailed safety information will emerge. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

TYRA-200 is unique because it offers a new approach to treating bile duct cancer. Unlike traditional chemotherapy, which targets rapidly dividing cells and can affect healthy cells too, TYRA-200 works by specifically targeting cancer cells with a novel mechanism of action. Researchers are excited about this treatment because it is taken orally, making it easier for patients compared to intravenous therapies, and it may offer fewer side effects. This targeted approach could lead to more effective outcomes and better quality of life for patients with this challenging condition.

What evidence suggests that TYRA-200 might be an effective treatment for bile duct cancer?

Research has shown that TYRA-200 targets changes in the FGFR2 gene, often found in bile duct cancer. FGFR2 is a protein that can promote cancer growth when altered. TYRA-200 blocks these changes, potentially slowing or stopping tumor growth. Early studies have shown promising results in various cancers with FGFR2 changes. Although human studies have provided limited information, the mechanism of TYRA-200 suggests it could benefit people with FGFR2-related cancers. Participants in this trial will take TYRA-200 orally once daily in 28-day cycles. ^{1 2 3 4 6}

Who Is on the Research Team?

Doug Warner

Principal Investigator

Tyra Biosciences, Inc

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including intrahepatic cholangiocarcinoma with FGFR2 gene alterations who have tried or declined standard treatments. For Part B, they must have had a prior FGFR inhibitor and specific resistance mutations. Exclusions include significant past anti-FGFR therapy toxicity, high serum phosphorus despite treatment, eye conditions increasing risk of toxicity, uncontrolled heart disease, active brain metastases, GI issues affecting drug absorption, and pregnant or breastfeeding women.

Inclusion Criteria

My advanced cancer has FGFR/FGF alterations and I've tried or refused all standard treatments.

My cancer has a specific mutation resistant to FGFR inhibitors, confirmed by an approved test.

I am fully active or can carry out light work.

Exclusion Criteria

My blood phosphorus levels are high despite treatment.

I do not have stomach or intestine problems affecting medication absorption.

I stopped a previous FGFR-targeted therapy due to severe side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A: Dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of TYRA-200 to determine the optimal and maximum tolerated dose

28-day cycles

Regular visits as per cycle

Antitumor Activity Evaluation

Part B: Evaluation of preliminary antitumor activity of TYRA-200 in participants with specific FGFR2 mutations

28-day cycles

Regular visits as per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TYRA-200

Trial Overview The trial is testing TYRA-200's safety and effectiveness against tumors with FGFR2 gene changes. Participants take the oral medication daily in 28-day cycles. The study has two parts: dose escalation (Part A) to find a safe dosage and dose expansion (Part B) to further assess its effects at that dosage.

How Is the Trial Designed?

Group I: Phase 1 Part A and Part B Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Tyra Biosciences, Inc

Lead Sponsor

Trials

4

Recruited

500+

Published Research Related to This Trial

In a study of 61 patients with biliary tract cancers, CYFRA 21-1 demonstrated a higher sensitivity (80.3%) compared to CA 19-9 (68.9%) for detecting these cancers, making it a more reliable biomarker.

CYFRA 21-1 levels increased progressively with the stage of the disease, indicating its potential to help differentiate between early and advanced stages of biliary malignancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of serum biomarkers cifra 21-1 and ca 19-9 in biliary tract cancers. Ghimire, B., Kansakar, PBS., Sngh, YP.[2022]

Cytotoxic therapy has limited effectiveness for advanced biliary tract and gallbladder cancers, highlighting the urgent need for new treatment options.

The development of targeted therapies that focus on growth factors and their receptors shows promise, especially when combined with existing cytotoxic drugs or other novel anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted medical therapy of biliary tract cancer: recent advances and future perspectives. Hopfner, M., Schuppan, D., Scherubl, H.[2023]

Bile survivin and carbohydrate antigen 199 (CA199) levels are significantly elevated in patients with cholangiocarcinoma, indicating their potential as biomarkers for this type of cancer.

The combination of bile survivin and CA199 improves the ability to differentiate cholangiocarcinoma from benign obstructive jaundice, with bile survivin showing a strong diagnostic capability (AUC of 0.780).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of bile survivin and carbohydrate antigen 199 in distinguishing cholangiocarcinoma from benign obstructive jaundice. Liu, Y., Sun, J., Zhang, Q., et al.[2018]

This study identified HER2 as a potential therapeutic target for biliary tract cancer (BTC), with 13% of advanced BTC patients being HER2-positive, suggesting a specific population that could benefit from targeted therapies.

In pre-clinical models, HER2-amplified BTC cell lines showed sensitivity to treatments like trastuzumab and dacomitinib, leading to significant anti-tumor effects, including increased apoptosis and cell cycle arrest, indicating promising efficacy for HER2-targeted strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic implication of HER2 in advanced biliary tract cancer. Nam, AR., Kim, JW., Cha, Y., et al.[2018]

Biliary drainage is crucial for palliative care in patients with non-resectable cholangiocarcinoma and gallbladder carcinoma, as it helps manage malignant biliary stenosis, which is common in these conditions.

Photodynamic therapy has shown improved median survival rates in patients with hilar cholangiocarcinoma, while the benefits of other treatments like external radiation and systemic chemotherapy remain uncertain and require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Palliative therapy in cholangio- and gallbladder carcinoma]. Klebl, F., Endlicher, E., Kullmann, F.[2015]

A study of 221 biliary tract carcinomas revealed that overexpression of tyrosine kinase receptors, particularly ErbB-2 and EGFR, is common, with ErbB-2 overexpressed in 15.7% of gall bladder carcinomas and associated with gene amplification in 79% of cases.

The findings suggest that targeting these overexpressed receptors with novel adjuvant chemotherapies could improve treatment options and patient outcomes for biliary tract carcinomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. Nakazawa, K., Dobashi, Y., Suzuki, S., et al.[2018]

In a study of 176 patients with advanced biliary tract cancer, the combination of capecitabine and cisplatin showed moderate efficacy, with a 17% partial response rate and a median overall survival of 7.4 months.

The study found that changes in CA19-9 levels were significantly correlated with both time-to-progression and overall survival, suggesting that CA19-9 could be a useful marker for monitoring treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective single-center study. Woo, SM., Lee, WJ., Han, SS., et al.[2015]

A case report highlights the successful use of HER2-targeted therapy with trastuzumab in a patient with HER2 positive distal common bile duct carcinoma, leading to a complete response and sustained remission.

The study utilized multi-analyte testing and in vitro chemosensitivity profiling to personalize the treatment regimen, combining trastuzumab with cyclophosphamide and methotrexate, showcasing a promising therapeutic approach for this rare cancer subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid biopsy and multi-analyte testing guided treatment of HER2 positive periampullary adenocarcinoma with durable complete response after trastuzumab based therapy. Nagarkar, R., Patil, D., Limaye, S., et al.[2020]

Resection of distal bile duct cancers significantly improves survival rates, with a mean survival of 22 months compared to 14 months for biliary bypass and 11 months for nonoperative intubation, based on a study of 156 patients.

The study found that a 5-year survival rate of 21% was achievable after resection for localized cancers, but no patients with nodal metastases survived beyond 3 years, highlighting the importance of early detection and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with distal bile duct cancers in U.S. Veterans Affairs hospitals: 1987-1991. Wade, TP., Prasad, CN., Virgo, KS., et al.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS646

A multicenter, open-label, first-in-human study of TYRA- ... TYRA-200 is an orally bioavailable FGFR1/2/3 inhibitor designed to specifically address these clinically observed acquired resistance alterations in FGFR2.

2. withpower.com withpower.com/trial/phase-1-locally-advanced-cholangiocarcinoma-10-2023-6ac70

TYRA-200 for Bile Duct Cancer (SURF201 Trial) Resection of distal bile duct cancers significantly improves survival rates, with a mean survival of 22 months compared to 14 months for biliary bypass and 11 ...

3. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/tyra-200-tyra-biosciences-bile-duct-cancer-cholangiocarcinoma-likelihood-of-approval/

TYRA-200 by Tyra Biosciences for Bile Duct Cancer ... TYRA-200 is under development for the treatment of FGFR2 mutated intrahepatic cholangiocarcinoma, endometrial cancer and solid tumors.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06160752

Safety and Anti-Tumor Activity of TYRA-200 in Advanced ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-200 in cancers with FGFR2 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10309532/

An Overview of Recent Approvals and Ongoing Clinical Trials Targetable alterations are found in up to 40%-50% of patients with intrahepatic cholangiocarcinoma and up to 15%-20% of patients with extrahepatic ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10638

Safety and Anti-Tumor Activity of TYRA-200 in Advanced ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-200 in cancers with FGFR2 ...