account_circleRecruiting

hepatocellular carcinoma

Bayer Identifier:

22262

ClinicalTrials.gov Identifier:

NCT06764316

EudraCT Number:

Not Available

EU CT Number:

2024-516615-25-00
A first-in-human study to learn about the safety of BAY 3547926 and how well it works in participants with advanced liver cancer

Trial purpose

In this study, researchers want to learn about the safety of a new drug, BAY 3547926, and how well the drug works in people with a type of liver cancer called advanced hepatocellular carcinoma (HCC). Researchers want to find the best dose of BAY 3547926 for people with advanced HCC and look at the way the body absorbs and distributes the drug.
The study drug, BAY 3547926, delivers a radioactive agent to cancer cells. The radioactive agent emits radiations which can damage the cancer cells and cause them to die. These radiations travel a small distance, so are expected to cause little damage to surrounding healthy tissues. This is the first study of BAY 3547926 in humans.
Participants will take part in one of the 3 different parts of the study. In Part 1, participants will receive different doses of BAY 3547926 alone to find the dose that is deemed safe and works best for the participants. When this dose has been found, a larger number of participants will receive BAY 3547926 alone in Part 2 or with other treatments in Part 3 of the study.
During the study, the doctors and their study team will do health check-ups, take pictures (scans) of the body, collect blood and urine samples, and ask participants questions about how they are feeling and what health problems they are having.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - Locally advanced or metastatic and/or unresectable HCC (hepatocellular carcinoma) with histological or cytological confirmation, or non-invasive diagnosis as per American Association for the Study of Liver Diseases (AASLD) criteria in participants with a confirmed diagnosis of cirrhosis.
    - Demonstrated molecular disposition by immunohistochemistry (IHC) on tumor sample.
    - Disease not amenable to, or progressive disease after, curative surgery and/or locoregional therapies of established efficacy such as resection, local ablation, chemoembolization.
    - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
    - At least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. as assessed by local site Investigator within 28 days prior to the start of the study treatment.
    - Adequate bone marrow and organ function
  • - Fibrolamellar HCC, sarcomatoid HCC, and mixed hepatocellular/cholangiocarcinoma subtypes.
    - Participants with a history or clinical evidence of CNS metastases, unless they meet specific criteria
    - History of encephalopathy ≥ Grade 2 within the past 12 months
    - Clinically significant ascites

Trial summary

Enrollment Goal
148
Trial Dates
February 2025 - December 2033
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY3547926
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Not yet recruiting
Princess Margaret Cancer Centre – University Health Network - Department of Medical Oncology and HematologyToronto, M5G 2C4, Canada
Recruiting
Centre Hospitalier de l'Universite de Montreal (CHUM) - HopiMontreal, H2X 0A9, Canada
Not yet recruiting
Royal Marsden NHS Foundation Trust | Sutton - Gastrointestinal UnitSutton, SM2 5PT, United Kingdom
Not yet recruiting
Imperial College LondonLondon, W12 0HS, United Kingdom
Not yet recruiting
McGill University Health Centre (MUHC) - Research Institute (RI) - McConnell Centre for Innovative Medicine (CIM)Montreal, H4A 3J1, Canada
Not yet recruiting
CIUSSS de l'Estrie-CHUSSherbrooke, J1H 5N4, Canada

Primary Outcome

  • Part 1 (dose escalation): Occurrence and severity of TEAEs
    TEAE=Treatment emergent adverse event
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 1 (dose escalation): Recommended safe and active dose (RSAD)
    The RSAD is based on incidence of DLT and preliminary anti-tumor activity (ORR using RECIST 1.1 by Investigator assessment) informed by TITE-CRM. RSAD=Recommended safe and active dose DLT=Dose limiting toxicity ORR=Objective reponse rate RECIST=Response Evaluation Criteria in Solid Tumors TITE-CRM =Time-to-event continual reassessment method
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 2 (dose expansion): Occurrence and severity of TEAEs
    TEAE=Treatment emergent adverse event
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 2 (dose expansion): ORR using RECIST 1.1 by investigator assessment
    ORR=Objective reponse rate RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 2 (dose expansion): DCR using RECIST 1.1 by investigator assessment
    DCR=Disease control rate RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 2 (dose expansion): DoR using RECIST 1.1 by investigator assessment
    DoR=Duration of response RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 2 (dose expansion): PFS using RECIST 1.1 by investigator assessment
    PFS=Progression free survival RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): Occurrence and severity of TEAEs
    TEAE=Treatment emergent adverse event
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): ORR using RECIST 1.1 by investigator assessment
    ORR= Objective response rate
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): DCR using RECIST 1.1 by investigator assessment
    DCR=Disease control rate
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): DoR using RECIST 1.1 by investigator assessment
    DoR=Duration of response
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): PFS using RECIST 1.1 by investigator assessment
    PFS=Progression free survivial
    date_rangeTime Frame:
    up to 60 months after first administration

Secondary Outcome

  • Part 1 (dose escalation): Recommended dose level(s) based on occurrence and severity of TEAEs and DLTs, PK, immunogenicity, and preliminary anit-tumor activity (ORR using RECIST 1.1 by Investigator assessment)
    TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic ORR=Objective response rate RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 1 (dose escalation): Recommended dosing regimen based on occurrence and severity of TEAEs and DLTs, PK, immunogenicity, and preliminary anti-tumor activity (ORR using RECIST 1.1 by Investigator assessment)
    TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic ORR=Objective response rate RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 1 (dose escalation): ORR using RECIST 1.1 by investigator assessment
    ORR=Objective response rate RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 1 (dose escalation): DCR using RECIST 1.1 by investigator assessment
    DCR=Disease control rate RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 1 (dose escalation): DoR using RECIST 1.1 by investigator assessment
    DoR=Duration of response RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    Up to 60 months after first administration
  • Part 1 (dose escalation): PFS using RECIST 1.1 by investigator assessment
    PFS=Progression free survival RECIST=Response Evaluation Criteria in Solid Tumors
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 1 (dose escalation): Cmax of BAY 3547926 after a single dose and after multiple doses
    Cmax=Maximal blood concentration
    date_rangeTime Frame:
    up to 36 weeks after first administration
  • Part 1 (dose escalation): AUC of BAY 3547926 after a single dose and after multiple doses
    AUC=Area under the blood concentration versus time curve
    date_rangeTime Frame:
    up to 36 weeks after first administration
  • Part 1 (dose escalation): Clearance of BAY 3547926 after a single dose and after multiple doses if data allow
    PK=Pharmacokinetic
    date_rangeTime Frame:
    up to 36 weeks after first administration
  • Part 2 (dose expansion): Recommended dose based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments
    PK=Pharmacokinetic IG=Immunogenicity
    date_rangeTime Frame:
    up to 36 months after first administration
  • Part 2 (dose expansion): Recommended schedule based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments
    PK=Pharmacokinetic IG=Immunogenicity
    date_rangeTime Frame:
    up to 36 months after first administration
  • Part 2 (dose expansion): Cmax of BAY 3547926 after a single dose and after multiple doses
    Cmax=maximal blood concentration
    date_rangeTime Frame:
    up to 36 weeks after first administration
  • Part 2 (dose expansion): AUC of BAY 3547926 after a single dose and after multiple doses
    AUC=Area under curve of blood concentration versus time curve
    date_rangeTime Frame:
    up to 36 weeks after first administration
  • Part 2 (dose expansion): Clearance of BAY 3547926 after single dose and after multiple doses, where applicable and if data allow
    PK=Pharmacokinetic
    date_rangeTime Frame:
    up to 36 weeks after first administration
  • Part 3 (dose expansion in combination): Recommended dose level(s) of BAY 3547926 based on clinical data including, but not limited to, occurrence and severity of TEAEs and DLTs, PK and IG
    TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic IG=Immunogenicity
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): Recommended dosing regimen of BAY 3547926 based on clinical data including, but not limited to, occurrence and severity of TEAEs and DLTs, PK and IG
    TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic IG=Immunogenicity
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): Recommended schedule of BAY 3547926 based on severity of TEAEs, PK, IG
    TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic IG=Immunogenicity
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): Cmax of BAY 3547926 after a single dose and after multiple doses of BAY 3547926 in combination
    Cmax=maximal blood concentration
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): AUC of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination
    AUC=Area under curve of blood concentration versus time curve
    date_rangeTime Frame:
    up to 60 months after first administration
  • Part 3 (dose expansion in combination): Clearance of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination, where applicable and if data allow
    PK=Pharmacokinetic
    date_rangeTime Frame:
    up to 60 months after first administration

Trial design

A multicenter, open label, non-randomized first-in-human phase 1 dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of BAY 3547926 alone, and in combination, in participants with advanced hepatocellular carcinoma (HCC)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Other
Allocation
N/A
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
1