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 4 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 Parts 3 and 4 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.
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.
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
Single group
BAY 3547926
Drugantibody conjugate with actinium-225 label
BAY 3547922
Drugantibody conjugate without actinium-225 label as preinjection
BAY 3713391
DrugRadioactive imaging agent - optional preinjection
Part 1 (dose escalation): Occurrence and severity of TEAEs
TEAE=Treatment emergent adverse event
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
Part 2 (dose expansion): Occurrence and severity of TEAEs
TEAE=Treatment emergent adverse event
Part 2 (dose expansion): ORR using RECIST 1.1 by investigator assessment
ORR=Objective reponse rate RECIST=Response Evaluation Criteria in Solid Tumors
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
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
Part 1 (dose escalation): ORR using RECIST 1.1 by investigator assessment
ORR=Objective response rate RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): DCR using RECIST 1.1 by investigator assessment
DCR=Disease control rate RECIST=Response Evaluation Criteria in Solid Tumors
