Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma (HCC), Locally advanced HCC, Metastatic HCC, Unresectable HCC
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 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.
Interventions
DRUGBAY 3547926
antibody conjugate with actinium-225 label
DRUGBAY 3547922
antibody conjugate without actinium-225 label as preinjection
DRUGBAY 3713391
Radioactive imaging agent - optional preinjection
DRUGBAY 3713389
optional preinjection
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (dose escalation): Occurrence and severity of TEAEs | up to 60 months after first administration | TEAE=Treatment emergent adverse event |
| 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 method |
| Part 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 |
| 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 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 |
| Parts 3 and 4 (dose expansion in combination): Occurrence and severity of TEAEs | up to 60 months after first administration | TEAE=Treatment emergent adverse event |
| Parts 3 and 4 (dose expansion in combination): ORR using RECIST 1.1 by investigator assessment | up to 60 months after first administration | ORR= Objective response rate |
| Parts 3 and 4 (dose expansion in combination): DCR using RECIST 1.1 by investigator assessment | up to 60 months after first administration | DCR=Disease control rate |
| Parts 3 and 4 (dose expansion in combination): DoR using RECIST 1.1 by investigator assessment | up to 60 months after first administration | DoR=Duration of response |
| Parts 3 and 4 (dose expansion in combination): PFS using RECIST 1.1 by investigator assessment | up to 60 months after first administration | PFS=Progression free survivial |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Parts 3 and 4 (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 |
| Parts 3 and 4 (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 |
| Parts 3 and 4 (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 |
| Parts 3 and 4 (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 |
| Parts 3 and 4 (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 |
| Parts 3 and 4 (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 |
Countries
Belgium, Canada, China, Finland, France, Japan, Spain, United Kingdom, United States
Contacts
CONTACTBayer Clinical Trials Contact
Outcome results
None listed