Clinical trial NCT06764316: A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma (HCC)
Locally advanced HCC
Metastatic HCC
Unresectable HCC
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2025-01-08
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1 (dose escalation): Occurrence and severity of TEAEs
timeFrame: up to 60 months after first administration
measure: Part 1 (dose escalation): Recommended safe and active dose (RSAD)
timeFrame: up to 60 months after first administration
measure: Part 2 (dose expansion): Occurrence and severity of TEAEs
timeFrame: up to 60 months after first administration
measure: Part 2 (dose expansion): ORR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 2 (dose expansion): DCR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 2 (dose expansion): DoR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 2 (dose expansion): PFS using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): Occurrence and severity of TEAEs
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): ORR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): DCR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): DoR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): PFS using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
Secondary outcomes:
measure: 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)
timeFrame: up to 60 months after first administration
measure: 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)
timeFrame: up to 60 months after first administration
measure: Part 1 (dose escalation): ORR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 1 (dose escalation): DCR using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 1 (dose escalation): DoR using RECIST 1.1 by investigator assessment
timeFrame: Up to 60 months after first administration
measure: Part 1 (dose escalation): PFS using RECIST 1.1 by investigator assessment
timeFrame: up to 60 months after first administration
measure: Part 1 (dose escalation): Cmax of BAY 3547926 after a single dose and after multiple doses
timeFrame: up to 36 weeks after first administration
measure: Part 1 (dose escalation): AUC of BAY 3547926 after a single dose and after multiple doses
timeFrame: up to 36 weeks after first administration
measure: Part 1 (dose escalation): Clearance of BAY 3547926 after a single dose and after multiple doses if data allow
timeFrame: up to 36 weeks after first administration
measure: Part 2 (dose expansion): Recommended dose based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments
timeFrame: up to 36 months after first administration
measure: Part 2 (dose expansion): Recommended schedule based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments
timeFrame: up to 36 months after first administration
measure: Part 2 (dose expansion): Cmax of BAY 3547926 after a single dose and after multiple doses
timeFrame: up to 36 weeks after first administration
measure: Part 2 (dose expansion): AUC of BAY 3547926 after a single dose and after multiple doses
timeFrame: up to 36 weeks after first administration
measure: Part 2 (dose expansion): Clearance of BAY 3547926 after single dose and after multiple doses, where applicable and if data allow
timeFrame: up to 36 weeks after first administration
measure: 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
timeFrame: up to 60 months after first administration
measure: 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
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): Recommended schedule of BAY 3547926 based on severity of TEAEs, PK, IG
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): Cmax of BAY 3547926 after a single dose and after multiple doses of BAY 3547926 in combination
timeFrame: up to 60 months after first administration
measure: Part 3 (dose expansion in combination): AUC of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination
timeFrame: up to 60 months after first administration
measure: 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
timeFrame: up to 60 months after first administration
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta - Cross Cancer Institute (CCI)
state: Alberta
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopi
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre (MUHC) - Research Institute (RI) - McConnell Centre for Innovative Medicine (CIM)
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie-CHUS
state: Quebec
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust | Sutton - Gastrointestinal Unit
state: Surrey
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
References: