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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug TYRA-200 for bile duct cancer?

The research highlights the potential of targeting tyrosine kinase growth factor receptors, like ErbB-2 and EGFR, which are overexpressed in some biliary tract cancers. This suggests that treatments targeting these receptors could be effective, although specific data on TYRA-200 is not provided. ^{1 2 3 4 5}

How is the drug TYRA-200 different from other treatments for bile duct cancer?

TYRA-200 is unique because it may target specific genetic markers like HER2, which is a potential therapeutic target in bile duct cancer, offering a new approach compared to traditional chemotherapy options. ^{1 6 7 8 9}

Research Team

Doug Warner

Principal Investigator

Tyra Biosciences, Inc

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Experience with distal bile duct cancers in U.S. Veterans Affairs hospitals: 1987-1991. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective single-center study. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Targeted medical therapy of biliary tract cancer: recent advances and future perspectives. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[Palliative therapy in cholangio- and gallbladder carcinoma]. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Identification of bile survivin and carbohydrate antigen 199 in distinguishing cholangiocarcinoma from benign obstructive jaundice. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Therapeutic implication of HER2 in advanced biliary tract cancer. [2018]

8. United States 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. [2020]

9. Nepal pubmed.ncbi.nlm.nih.gov

Comparison of serum biomarkers cifra 21-1 and ca 19-9 in biliary tract cancers. [2022]