TYRA-430 for Liver Cancer

(SURF431 Trial)

Recruiting at 4 trial locations

Overseen By Grace Indyk

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tyra Biosciences, Inc

Must not be taking: Immunotherapy, Antibody therapy, TKI

Disqualifiers: Uncontrolled 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

100 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain anticancer therapies within specific time frames before starting the study drug.

What data supports the effectiveness of the drug TYRA-430 for liver cancer?

Research shows that tyroserleutide, a component similar to TYRA-430, can slow down the growth and spread of liver cancer in both lab and animal studies. Additionally, targeting Tyro3, which is related to TYRA-430, has been shown to reduce liver cancer cell growth, suggesting potential effectiveness. ^{1 2 3 4 5}

What safety information is available for TYRA-430 or similar treatments for liver cancer?

While specific safety data for TYRA-430 is not available, similar treatments like tyrosine kinase inhibitors (TKIs) used for liver cancer can cause side effects such as fatigue, diarrhea, skin reactions, nausea, and high blood pressure. These treatments can also increase the risk of serious and potentially fatal adverse events, so careful management and monitoring are important. ^{6 7 8 9 10}

How does the drug TYRA-430 differ from other liver cancer treatments?

The research does not provide specific information about TYRA-430, but it highlights the role of Farnesoid X receptor (FXR) in liver cancer treatment. FXR regulates bile acid metabolism and has a hepatoprotective role, which could be a unique mechanism if TYRA-430 involves FXR modulation. ^{11 12 13 14 15}

What is the purpose of this trial?

A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers with FGF/FGFR pathway aberrations, including locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors.

Research Team

Doug Warner, MD

Principal Investigator

Tyra Biosciences, Inc

Eligibility Criteria

This trial is for adults with advanced liver cancer or other solid tumors that have specific genetic changes in the FGF/FGFR pathway. Participants should not have received certain treatments before and must be able to take oral medication.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

I can swallow pills.

My liver function is good.

Exclusion Criteria

I have brain metastases that are causing symptoms or haven't been treated.

Any reason that, in the view of investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant

My liver cancer is of a specific rare type.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of TYRA-430 as monotherapy at various dose levels to determine the maximum tolerated dose

Up to 1 year

Dose Expansion

Dose expansion group for TYRA-430 monotherapy in advanced solid tumors and advanced HCC at a dose(s) determined in Part A

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after the last dose

Treatment Details

Interventions

• TYRA-430

Trial Overview The study tests TYRA-430, a new drug, on its safety and early signs of effectiveness against tumors. It's given to patients with particular genetic tumor profiles linked to the FGF/FGFR pathway.

Participant Groups

Group I: Part B - Cohort 2 Dose Expansion Experimental Treatment 1 Intervention

Dose expansion group for TYRA-430 monotherapy in advanced solid tumors at a dose(s) determined in Part A.

Group II: Part B - Cohort 1 Dose Expansion Experimental Treatment 1 Intervention

Dose expansion group for TYRA-430 monotherapy in advanced HCC at a dose(s) determined in Part A.

Group III: Part A - Dose Escalation Experimental Treatment 1 Intervention

Dose escalation of TYRA-430 as monotherapy at various dose levels.

Who Is Running the Clinical Trial?

Tyra Biosciences, Inc

Lead Sponsor

Trials

4

Recruited

500+

Findings from Research

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

Recent cancer treatments, including monoclonal antibodies and kinase inhibitors, have been developed to specifically target cancer pathways, showing promise in improving cancer control.

However, these therapies are associated with significant gastrointestinal and hepatic toxic effects, such as diarrhea and liver damage, which can lead to treatment discontinuation and reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug insight: gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy. Loriot, Y., Perlemuter, G., Malka, D., et al.[2016]

References

1. China pubmed.ncbi.nlm.nih.gov

[Tyroservatide inhibits the growth of human hepatocarcinoma in nude mice]. [2006]

2. Germany pubmed.ncbi.nlm.nih.gov

Experimental study of the inhibition of human hepatocarcinoma Bel7402 cells by the tripeptide tyroserleutide(YSL). [2016]

3. Greece pubmed.ncbi.nlm.nih.gov

Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression. [2016]

4. Greece pubmed.ncbi.nlm.nih.gov

Study on the inhibitory effect of tyroserleutide on tumor growth and metastasis in nude mice model of human hepatocellular carcinoma metastasis. [2016]

5. Greece pubmed.ncbi.nlm.nih.gov

TYRO3 as a potential therapeutic target in breast cancer. [2016]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapies for advanced hepatocellular carcinoma. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with tyrosine kinase inhibitors: Improving outcomes for patients with hepatocellular carcinoma. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Immunotherapy combination with regorafenib for refractory hepatocellular carcinoma: A real-world study. [2022]

9. India pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Drug insight: gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Cholangiopancreatography to Evaluate Improvement Effect of FXR Regulating Bile Acid on Hepatocellular Carcinoma with Obstructive Jaundice. [2022]

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

Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Activation of FXR modulates SOCS3/Jak2/STAT3 signaling axis in a NASH-dependent hepatocellular carcinoma animal model. [2021]

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

Manipulating Liver Bile Acid Signaling by Nanodelivery of Bile Acid Receptor Modulators for Liver Cancer Immunotherapy. [2021]

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

Chronic Activation of LXRα Sensitizes Mice to Hepatocellular Carcinoma. [2023]