Comparing 3 approaches for metastatic hepatocellular carcinoma
Official title: Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
A Multicenter, Open-label, First-in-Human Study of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
- Phase 1
- 3 groups
- One site, in Toronto
- Recruiting
Interventions
- Medication
TYRA-430
Oral TYRA-430 given daily.
Canadian Sites (1)
1 of 1 recruiting
- Recruiting
University Health Network Princess Margaret Cancer Center
Toronto, Ontario
Eligibility Criteria
See who this study is looking for44 criteria
The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.
Inclusion
- +Age ≥ 18 years
- +Must have an eligible activating gain-of-function alteration in the FGFR3 or FGFR4 gene, or focal amplifications of FGF19
- +All Patients:
- +Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- +Adequate end organ function.
- +Ability to swallow oral formulations.
- +Ability to understand and willingness to sign the ICFInformed consentThe process of being told what taking part involves, then choosing freely.Read more →.
- +Histologically confirmed locally advanced unresectable/metastatic HCC or histologically confirmed advanced solid tumor with documented FGF/FGFR pathway alterations
- +For participants with histologically confirmed locally advanced or metastatic HCC:
- +Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.
- +Child-Pugh Score class A
- +Must have previously received SOCStandard of careThe treatment normally given for a condition outside a study.Read more → appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted.
- +Agree to provide archival tumor tissue no older than 2 years from the time of enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →, if available. If an archived specimen is not available, a biopsy is not required.
- +Part B, CohortCohortA group of participants sharing a characteristic, followed together.Read more → 1:
- +Histologically confirmed locally advanced/metastatic HCC who have previously received standard of care.
- +Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.
- +Child-Pugh Score class A
- +Availability of an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen obtained ≤2 years prior to screeningScreeningThe checks done before joining, to see whether a study fits.Read more → for submission to sponsorSponsorThe organisation responsible for the study overall.Read more →-designated central laboratory for FGF19 IHC testing.
- +At least 1 measurable lesion by RECIST v1.1.
- +Part B, Cohort 2:
- +Histologically confirmed advanced solid tumor except FGFR3-altered urothelial carcinoma and primary central nervous system tumors who have previously received standard of care. Note: Participants with confirmed diagnosis of locally advanced or metastatic HCC are not eligible for Cohort 2.
- +Archival tumor tissue biopsy specimen no older than 2 years from the time of enrollment, if available. If a tissue biopsy specimen is not available, a biopsy is not required.
- +At least 1 measurable lesion by RECIST v1.1.
Exclusion
- −Active, symptomatic, or untreated brain metastases.
- −All Patients:
- −Have disease that is suitable for local therapy administered with curative intent.
- −Have not recovered from reversible toxicity of prior anticancer therapy to \< Grade 1 or baselineBaselineYour starting measurements, taken before treatment begins.Read more → (except toxicities that are not clinically significant or not expected to resolve, including but not limited to, alopecia, fatigue, skin discoloration, or Grade 1 neuropathy).
- −Have received the following anticancer therapy:
- −A TKI \< 5 days or 5X the terminal Phase elimination half-lives, whichever is longer, prior to the first dose of TYRA-430.
- −Other systemic therapy not listed above \< 14 days prior to the first dose of the study drug.
- −Participant 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 screeningScreeningThe checks done before joining, to see whether a study fits.Read more → that remains \>ULN despite medical management.
- −History of or current uncontrolled cardiovascular disease.
- −Have a diagnosis of primary CNS malignancies.
- −Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430.
- −Any reason that, in the view of investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant.
- −Part B, CohortCohortA group of participants sharing a characteristic, followed together.Read more → 1:
- −Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- −Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors.
- −Part B, Cohort 2:
- −Histologically confirmed locally advanced/metastatic HCC.
- −Histologically confirmed urothelial cancer.
- −Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolledEnrolmentThe number of participants a study plans to include, or has included.Read more → in this study.
- −Any immunotherapy or other antibody therapy within 28 days prior to the first dose of the study drug.
In plain language
Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.
What this study is
This study is testing a treatment for a condition.
Phase 1Phase 1The earliest stage of human testing, in a small group, focused on safety.Read more → — an early safety study in a small group, checking how it is tolerated and at what dose.
From the trial registry
Built from these fields:
- designModule.designInfo.primaryPurpose
- designModule.phases
Who receives what
There are 3 groups in this study.
Groups A, B and C receive TYRA-430.
Registry label: A: Part A - Dose Escalation · B: Part B - Cohort 1 Dose Expansion · C: Part B - Cohort 2 Dose Expansion
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].label
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
How the study is run
Groups are assigned by the study team using set rules, rather than by chance.
This study is open-labelOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more →: everyone knows which treatment is being given, including you and the study team.
From the trial registry
Built from these fields:
- designModule.designInfo.allocation
- designModule.designInfo.maskingInfo.masking
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
Who the study is looking for
The study lists a minimum age of 18 years, with no upper limit given.
The study is open to people of any sex.
The study does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
These are the criteria the study lists. Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part.
From the trial registry
Built from these fields:
- eligibilityModule.minimumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How big and how long
The study aims to enrol about 100 people.
The study is currently expected to finish around September 2028.
The main measurement is taken over: Up to 1 year.
From the trial registry
Built from these fields:
- designModule.enrollmentInfo.count
- statusModule.completionDateStruct.date
- outcomesModule.primaryOutcomes[].timeFrame
What the study measures
Maximum tolerated doseMaximum tolerated doseThe highest amount that can be given before side effects become unacceptable.Read more → (MTD) — measured over Up to 1 year.
Rate and severity of adverse eventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → of TYRA-430 as monotherapy — measured over First dose of study drug through 28 days after the last dose of study drug.
Recommended Phase 2Phase 2A middle-stage study looking at what a treatment does and watching for side effects.Read more → dose(s) of TYRA-430 — measured over Up to 2 years.
From the trial registry
Built from these fields:
- outcomesModule.primaryOutcomes[].measure
- outcomesModule.primaryOutcomes[].timeFrame
Source: NCT06915753 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.
Not medical advice. What do these terms mean?
What is being tested — in plain terms
About TYRA-430Drug
Oral TYRA-430 given daily.
From the trial registry — its own words, unedited.
What a drug is here: A medicine — a chemical or small-molecule treatment — given as the thing being studied.
Read the full explanation → · in clinical review
Common questions
Answered from this trial’s registry record. Where the record doesn’t say, these answers say so rather than filling the gap.
Am I eligible for this trial?
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part. Concord cannot make that determination, and neither can any tool that has not examined you.
What the study lists: a minimum age of 18 years.
The full inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → and exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → are published on this page, exactly as the study team wrote them.
The useful next step is to bring this trial to your doctor. Answering a few questions first gives them something concrete to review.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.eligibilityCriteria
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
From the trial registry
- armsInterventionsModule.armGroups[].type
Would I know which treatment I am getting?
This study is open-labelOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more →: everyone knows which treatment is being given, including you and the study team.
Groups are assigned by the study team using set rules, rather than by chance.
From the trial registry
- designModule.designInfo.maskingInfo.masking
- designModule.designInfo.allocation
Who can join?
The study lists a minimum age of 18 years, with no upper limit given.
It is open to people of any sex.
It does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can confirm whether a particular person can take part.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How long would this take?
The study's main measurement is taken over: Up to 1 year.
The study as a whole is currently expected to finish around 2028-09.
How long any one person takes part can differ from the study length. The study team can tell you what the schedule looks like in practice.
From the trial registry
- outcomesModule.primaryOutcomes[].timeFrame
- statusModule.completionDateStruct.date
How many people are taking part?
The study aims to enrol about 100 people.
From the trial registry
- designModule.enrollmentInfo.count
Where is this happening?
This study lists 3 locations, including: Toronto, Ontario, Canada; Detroit, Michigan, United States; New York, New York, United States.
Sites can open and close during a study, so confirm with the team before travelling.
From the trial registry
- trial_locations
About 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.
Other Sites (2)
Karmanos Cancer Institute
Detroit, Michigan, United States
Columbia University Irving Medical Center
New York, New York, United States
Think this trial might be right for you?
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See if this trial could fit youThis page is for informational purposes only and does not constitute medical advice. Clinical trial eligibility can only be determined by the trial site after proper screening. Trial information is sourced from ClinicalTrials.gov and may not reflect the most current status. Always consult your healthcare provider before making decisions about clinical trial participation.