BAY3630942 After BAY3547922 for Liver Cancer

Recruiting at 6 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bayer

Must be taking: LHRH agonists

Must not be taking: Systemic anticancer therapy

Disqualifiers: Cardiac disease, Thrombotic events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on ongoing systemic anticancer therapy, except for certain prostate cancer treatments.

What safety information is available for regorafenib in liver cancer treatment?

Regorafenib, used for liver cancer, has been associated with side effects like diarrhea, fatigue, and skin reactions on hands and feet. It can also cause liver-related issues, such as increased liver enzymes and bilirubin, which are indicators of liver stress or damage. ^{1 2 3 4 5}

What is the purpose of this trial?

Researchers are studying a new potential treatment for liver cancer or other select solid cancers. To do this, researchers have developed a protein, called a monoclonal antibody, which can find and attach itself to another protein present on the surface of cancer cells. This can help the new treatment to specifically target cancer cells. In this study, researchers want to understand the distribution and processing of this monoclonal antibody in people with liver cancer or other select solid cancers. Researchers will use the following two forms of monoclonal antibody as study interventions during this study: * BAY3630942: This is the monoclonal antibody attached to a tracer. A tracer emits radiation that can help researchers track the monoclonal antibody in the body using imaging tests like PET/CT (positron emission tomography / computed tomography). All participants will receive a fixed dose of BAY3630942 during the study. * BAY3547922: This is the monoclonal antibody without the tracer. Participants may receive different amounts of BAY3547922 during the study. In this study, participants will not derive therapeutic benefit from receiving BAY3630942 or BAY3547922. However, this study may help researchers develop a new treatment for people with liver cancer or other select solid cancers and find a dose to be tested in future studies. The main purpose of this first-in-human study is to check how BAY3630942 distributes among different organs in the body and how much of the radiation it emits is absorbed by the organs based on the total dose of BAY3630942 and BAY3547922 given. For this, the researchers will: * measure the amount of BAY3630942 radiation found in different organs over time. * measure the amount of BAY3630942 radiation absorbed by different organs. * use the above information to estimate the amount of radiation that would be absorbed by the same organs from the new potential treatment. Researchers will also monitor the number and severity of medical problems participants have after receiving BAY3630942 and BAY3547922. These medical problems are also known as "adverse events". Doctors keep track of all medical problems that happen in studies, even if they do not think they might be related to the study interventions. The study participants will first receive BAY3547922 as an infusion into a vein followed by BAY3630942 as an injection into the same vein. Both interventions will be administered only once, on the same day. Each participant will be in the study for around 44 days with up to 7 visits to the study clinic which includes: * a visit up to 14 days before the start of the study to confirm if the participant can take part in the study. * up to 5 visits during the imaging intervention period. During this period, participants: * will receive the study interventions and have blood tests on the first visit, * will have imaging and blood tests on the next 3 visits. The tests scheduled for the second visit may be performed during the first visit. * may have blood tests on the last visit. * a follow-up visit to check their health after 30 days of receiving the study interventions. During the study, the doctors and their study team will: * check participants' health by performing tests such as blood and urine tests, and check heart health using an electrocardiogram (ECG) * track and study BAY3630942 using PET/CT imaging tests As the study interventions are not yet treatments for liver cancer or other select solid cancers, access to BAY3630942 and BAY3547922 after the end of the study will not be required.

Eligibility Criteria

This trial is for individuals with liver cancer. Participants will receive two monoclonal antibodies, one with a tracer (BAY3630942) and one without (BAY3547922), to study how they distribute in the body. The goal is not treatment but to inform future dose selection.

Inclusion Criteria

My liver cancer diagnosis is confirmed by lab tests or meets specific criteria.

Able to tolerate the study procedures, including 3 PET/CT scans

Agreed to take proper contraception measures

Exclusion Criteria

I do not have serious heart problems like heart failure.

Any condition which, in the opinion of the Investigator, would preclude participation in this study

I haven't had a treatment with a radioisotope like yttrium-90 within the last 24 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Imaging Intervention

Participants receive BAY3547922 and BAY3630942, followed by imaging and blood tests

12 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

Treatment Details

Interventions

• BAY3547922
• BAY3630942

Trial Overview Researchers are testing BAY3630942 and BAY3547922 in people with liver cancer to understand their distribution within the body using PET/CT imaging. This first-in-human study aims to track these substances and assess safety over approximately 44 days.

Participant Groups

Group I: Part 2 - Actinium-225 Dosimetry Estimates Experimental Treatment 2 Interventions

Participants with HCC or other select solid tumors will receive the total mass dose level selected in Part 1.

Group II: Part 1 - Total mass dose selection Experimental Treatment 2 Interventions

Participants with HCC or other select solid tumors will receive a single dose of BAY3630942 after intravenous (IV) administration of a specified dose of BAY3547922. Up to 5 total mass dose levels may be tested.

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

Regorafenib has demonstrated a median overall survival of 11.08 months in hepatocellular carcinoma patients who have failed sorafenib treatment, based on a meta-analysis of 809 patients from one randomized-controlled trial and seven non-randomized studies.

The treatment shows a disease control rate of 65.5% and is considered relatively safe, with common side effects including diarrhea, fatigue, and hand-foot skin reactions, making it a valuable option for patients with intermediate to advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis. Facciorusso, A., Abd El Aziz, MA., Sacco, R.[2023]

A meta-analysis of 2,213 subjects from 14 trials revealed that regorafenib, an oral multi-kinase inhibitor, significantly increases the risk of hepatic toxicities, with notable elevations in liver enzymes such as AST (32% incidence) and ALT (27% incidence).

Patients treated with regorafenib showed a high-grade risk of bilirubin elevation (5%) and AST elevation (6%), indicating the need for regular monitoring of liver function during treatment to manage potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk of regorafenib-induced hepatotoxicity. Zhao, B., Zhao, H.[2019]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

Hepatitis B reactivation can occur in patients undergoing cytotoxic chemotherapy, including those treated with everolimus, leading to severe liver complications, as illustrated by a fatal case in a woman with metastatic breast cancer.

It is crucial for clinicians to screen for hepatitis B and consider prophylactic antiviral treatment before starting everolimus, as this rare but serious complication can arise even in patients with resolved or inactive hepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature. Teplinsky, E., Cheung, D., Weisberg, I., et al.[2015]

Regorafenib significantly improves overall survival in patients with advanced hepatocellular carcinoma (HCC) who have previously been treated with sorafenib, with a median overall survival of 10.6 months compared to 7.8 months for placebo, based on a randomized trial involving these patients.

The drug also shows a notable improvement in progression-free survival (3.1 months for regorafenib vs. 1.5 months for placebo) and has an acceptable safety profile, making it a promising new standard of care for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Summary of Regorafenib for the Treatment of Patients with Advanced Hepatocellular Carcinoma That Has Progressed on Sorafenib. Pelosof, L., Lemery, S., Casak, S., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Incidence and risk of regorafenib-induced hepatotoxicity. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Benefit-Risk Summary of Regorafenib for the Treatment of Patients with Advanced Hepatocellular Carcinoma That Has Progressed on Sorafenib. [2019]