TYRA-430 for Liver Cancer

(SURF431 Trial)

Recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests TYRA-430, a new treatment for liver cancer and other advanced solid tumors with specific genetic changes. Researchers aim to determine the safety of TYRA-430 and its effects on the body and cancer growth. The trial includes different phases to identify the optimal dose and assess its effectiveness in patients. It seeks participants with liver cancer who cannot undergo surgery or other local treatments and have previously received standard treatments. Participants should be able to eat normally and have a specific type of liver cancer or other tumors with certain genetic traits. As a Phase 1 trial, this research focuses on understanding how TYRA-430 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that TYRA-430 is likely to be safe for humans?

Research has shown that TYRA-430 holds promise in early studies, particularly in liver cancer models. These studies examined the drug's effects on cancer cells both in the lab and in living organisms. In these controlled settings, TYRA-430 effectively targeted cancer cells.

As TYRA-430 undergoes its first human trials, information on its effects in people remains limited. However, these early studies are crucial for understanding potential side effects and patient tolerance. At this stage, the primary focus is on ensuring the treatment's safety and gathering initial data on how the body processes the drug.

The studies aim to identify the safest and most effective dose of TYRA-430 for treating liver cancer and other solid tumors. Participants in these studies help researchers learn more about the drug's safety, including any side effects it might cause. This information is essential for determining if TYRA-430 can become a safe and effective cancer treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver cancer?

Unlike standard treatments for liver cancer, which often include chemotherapy and targeted therapies like sorafenib, TYRA-430 offers a new approach. TYRA-430 is unique because it targets specific mutations in cancer cells, potentially leading to more precise and effective treatment outcomes. Researchers are excited about its ability to selectively attack cancerous cells while sparing healthy ones, which could mean fewer side effects for patients. This innovative mechanism of action sets TYRA-430 apart and holds promise for improving the quality of life for those battling advanced liver cancer.

What evidence suggests that TYRA-430 might be an effective treatment for liver cancer?

Research has shown that TYRA-430 may help treat liver cancer, specifically hepatocellular carcinoma (HCC). In studies with mice implanted with human liver cancer cells, TYRA-430 reduced tumor growth by 96%, a significant improvement over another treatment that reduced growth by 75%. TYRA-430 targets a specific part of cancer cells that aids their growth. Early results suggest it could effectively slow liver cancer and possibly other solid tumors. Participants in this trial will receive TYRA-430 as monotherapy, with dose escalation and expansion phases to determine its effectiveness and optimal dosing. ^{1 3 6 7 8}

Who Is on the Research Team?

Doug Warner, MD

Principal Investigator

Tyra Biosciences, Inc

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.583

TYRA-430: First reversible FGFR4/3 inhibitor designed to ... Furthermore, in a human HuH-7 HCC xenograft model in nu/nu mice, TYRA-430 achieved 96% tumor growth inhibition (TGI), compared to 75% TGI for ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06915753

Safety and Preliminary Anti-Tumor Activity of TYRA-430 in ... A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers ...

3. bioworld.com bioworld.com/articles/717034-tyra-biosciences-tyra-430-exerts-antitumoral-effects-in-hcc

Tyra Biosciences' TYRA-430 exerts antitumoral effects in ... In vivo, using the human HuH-7 HCC xenografted model in mice, TYRA-430 demonstrated 96% tumor growth inhibition (TGI), which was greater than 75 ...

4. ir.tyra.bio ir.tyra.bio/static-files/704ed97f-4671-4908-b84f-a20e9e109b6c

Mohamed A. Ahmed, Jacqueline H. Starrett, Isaac Hoffman, ... The Phase 1 clinical study (SURF431) will evaluate TYRA-430 in patients with advanced hepatocellular carcinoma (HCC) and other solid tumors with FGF/FGFR ...

5. withpower.com withpower.com/trial/phase-1-fgfr3-gene-alteration-3-2025-a87ad

TYRA-430 for Liver Cancer (SURF431 Trial) 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.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)01636-9/fulltext

288eTiP A multicenter, open-label, first-in-human study of ... SURF431 (NCT06915753) is a first-in-human, open-label, phase 1 global study designed to explore TYRA-430 as monotherapy in patients with advanced HCC and other ...

7. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/multicenter-open-label-first-human-study-tyra-430-advanced-hepatocellularcarcinoma-and-other-solid-tumors-activating-fgf-fgfr-pathway-aberrations-surf-431

A Multicenter, Open-label, First-in-Human Study of TYRA-430 ... The purpose of this Study is to find out if an investigational drug, TYRA-430, is safe and effective at treating cancer in participants with locally ...

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06915753/safety-and-preliminary-anti-tumor-activity-of-tyra-430-in-advanced-hepatocellular-carcinoma-and-other-solid-tumors-with-activating-fgf-fgfr-pathway-aberrations?state=CT&city=Standord

Safety and Preliminary Anti-Tumor Activity of TYRA-430 in ... A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA- ...