A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer
- Registration Number
- NCT06764316
- Lead Sponsor
- Bayer
- Brief Summary
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), which has a special protein called Glypican 3 (GPC3). 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 148
- 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 positive centrally confirmed GPC3 expression 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BAY 3547926 BAY 3547922 actinium-225 labeled antibody conjugate BAY 3547926 BAY 3547926 actinium-225 labeled antibody conjugate
- Primary Outcome Measures
Name Time Method Part 2 (dose expansion): DCR using RECIST 1.1 by investigator assessment up to 60 months after first administration DCR=Disease control rate RECIST=Response Evaluation Criteria in Solid Tumors
Part 2 (dose expansion): DoR using RECIST 1.1 by investigator assessment up to 60 months after first administration DoR=Duration of response RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): Occurrence and severity of TEAEs up to 60 months after first administration TEAE=Treatment emergent adverse event
Part 2 (dose expansion): PFS using RECIST 1.1 by investigator assessment up to 60 months after first administration PFS=Progression free survival RECIST=Response Evaluation Criteria in Solid Tumors
Part 3 (dose expansion in combination): Occurrence and severity of TEAEs up to 60 months after first administration TEAE=Treatment emergent adverse event
Part 3 (dose expansion in combination): ORR using RECIST 1.1 by investigator assessment up to 60 months after first administration ORR= Objective response rate
Part 3 (dose expansion in combination): DCR using RECIST 1.1 by investigator assessment up to 60 months after first administration DCR=Disease control rate
Part 3 (dose expansion in combination): DoR using RECIST 1.1 by investigator assessment up to 60 months after first administration DoR=Duration of response
Part 3 (dose expansion in combination): PFS using RECIST 1.1 by investigator assessment up to 60 months after first administration PFS=Progression free survivial
Part 1 (dose escalation): Recommended safe and active dose (RSAD) up to 60 months after first administration 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 methodPart 2 (dose expansion): Occurrence and severity of TEAEs up to 60 months after first administration TEAE=Treatment emergent adverse event
Part 2 (dose expansion): ORR using RECIST 1.1 by investigator assessment up to 60 months after first administration ORR=Objective reponse rate RECIST=Response Evaluation Criteria in Solid Tumors
- Secondary Outcome Measures
Name Time Method 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) up to 60 months after first administration TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic ORR=Objective response rate RECIST=Response Evaluation Criteria in Solid Tumors
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) up to 60 months after first administration TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic ORR=Objective response rate RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): ORR using RECIST 1.1 by investigator assessment up to 60 months after first administration ORR=Objective response rate RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): DCR using RECIST 1.1 by investigator assessment up to 60 months after first administration DCR=Disease control rate RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): DoR using RECIST 1.1 by investigator assessment Up to 60 months after first administration DoR=Duration of response RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): PFS using RECIST 1.1 by investigator assessment up to 60 months after first administration PFS=Progression free survival RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): Cmax of BAY 3547926 after a single dose and after multiple doses up to 36 weeks after first administration Cmax=Maximal blood concentration
Part 1 (dose escalation): AUC of BAY 3547926 after a single dose and after multiple doses up to 36 weeks after first administration AUC=Area under the blood concentration versus time curve
Part 1 (dose escalation): Clearance of BAY 3547926 after a single dose and after multiple doses if data allow up to 36 weeks after first administration PK=Pharmacokinetic
Part 2 (dose expansion): Recommended dose based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments up to 36 months after first administration PK=Pharmacokinetic IG=Immunogenicity
Part 2 (dose expansion): Recommended schedule based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments up to 36 months after first administration PK=Pharmacokinetic IG=Immunogenicity
Part 2 (dose expansion): Cmax of BAY 3547926 after a single dose and after multiple doses up to 36 weeks after first administration Cmax=maximal blood concentration
Part 2 (dose expansion): AUC of BAY 3547926 after a single dose and after multiple doses up to 36 weeks after first administration AUC=Area under curve of blood concentration versus time curve
Part 2 (dose expansion): Clearance of BAY 3547926 after single dose and after multiple doses, where applicable and if data allow up to 36 weeks after first administration PK=Pharmacokinetic
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 up to 60 months after first administration TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic IG=Immunogenicity
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 up to 60 months after first administration TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic IG=Immunogenicity
Part 3 (dose expansion in combination): Recommended schedule of BAY 3547926 based on severity of TEAEs, PK, IG up to 60 months after first administration TEAE=Treatment emergent adverse event DLT=Dose limiting toxicity PK=Pharmacokinetic IG=Immunogenicity
Part 3 (dose expansion in combination): Cmax of BAY 3547926 after a single dose and after multiple doses of BAY 3547926 in combination up to 60 months after first administration Cmax=maximal blood concentration
Part 3 (dose expansion in combination): AUC of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination up to 60 months after first administration AUC=Area under curve of blood concentration versus time curve
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 up to 60 months after first administration PK=Pharmacokinetic
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (8)
Tampere University Hospital
🇫🇮Tampere, Finland
Turku University Hospital
🇫🇮Turku, Finland
University of Alberta - Cross Cancer Institute (CCI)
🇨🇦Edmonton, Alberta, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopi
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre (MUHC) - Research Institute (RI) - McConnell Centre for Innovative Medicine (CIM)
🇨🇦Montreal, Quebec, Canada
CIUSSS de l'Estrie-CHUS
🇨🇦Sherbrooke, Quebec, Canada
Royal Marsden NHS Foundation Trust | Sutton - Gastrointestinal Unit
🇬🇧Sutton, Surrey, United Kingdom
Imperial College London
🇬🇧London, United Kingdom