A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer

Phase 1RecruitingNCT06764316

Bayer148 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

148

Conditions

Hepatocellular Carcinoma

Interventions

BAY 3547926DRUG

antibody conjugate with actinium-225 label

BAY 3547922DRUG

antibody conjugate without actinium-225 label as preinjection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (10)

UZA - Digestive Oncology

Edegem, Belgium

RECRUITING

az Groeninge - Digestive Oncology

Kortrijk, Belgium

RECRUITING

Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopi

Montreal, Quebec, Canada

RECRUITING

McGill University Health Centre (MUHC) - Research Institute (RI) - McConnell Centre for Innovative Medicine (CIM)

Montreal, Quebec, Canada

RECRUITING

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, Canada

RECRUITING

Tampere University Hospital, Cancer Center

Tampere, Finland

RECRUITING

Turku University Hospital - Oncology Department

Turku, Finland

RECRUITING

The START Center for Cancer Care - Madrid - CIOCC - Hospital Universitario Madrid Sanchinarro - Oncologia

Madrid, Spain

RECRUITING

Royal Marsden NHS Foundation Trust | Sutton - Gastrointestinal Unit

Sutton, Surrey, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust | Hammersmith Hospital - Garry Weston Centre

London, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

Part 1 (dose escalation): Occurrence and severity of TEAEs

TEAE=Treatment emergent adverse event

Time 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

Time frame: up to 60 months after first administration

Part 2 (dose expansion): Occurrence and severity of TEAEs

TEAE=Treatment emergent adverse event

Time 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

Time 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

Time 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

Time 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

Time frame: up to 60 months after first administration

Part 3 (dose expansion in combination): Occurrence and severity of TEAEs

TEAE=Treatment emergent adverse event

Time 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

Time 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

Time 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

Time 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

Time frame: up to 60 months after first administration

Secondary Outcomes

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

Time 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

Time 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

Time 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

Time 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

Time 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

Time frame: up to 60 months after first administration

Part 1 (dose escalation): Cmax of BAY 3547926 after a single dose and after multiple doses

Central Contacts

Bayer Clinical Trials Contact

CONTACT

(+)1-888-84 22937 clinical-trials-contact@bayer.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Cmax=Maximal blood concentration

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time 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

Time frame: up to 60 months after first administration