BAY3630942 After BAY3547922 for Liver Cancer

Recruiting in Palo Alto (17 mi)

+6 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Bayer

Must be taking: LHRH agonists

Must not be taking: Systemic anticancer therapy

Disqualifiers: Cardiac disease, Thrombotic events, others

No Placebo Group

Trial Summary

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.

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.

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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.

I am 18 years old or older.

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

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.

Trial 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)

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

City of Hope - Duarte Cancer Center Duarte, CA

University of Southern California (USC) - Norris Comprehensive Cancer Center Los Angeles, CA

City of Hope National Medical Center Duarte, CA

HonorHealth Research Institute Scottsdale, AZ

More Trial Locations

Who Is Running the Clinical Trial?

Bayer Lead Sponsor

References

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

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis. [2023] Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46-12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68-3.86). The pooled objective response rate was 10.1% (7.8%-12.5%) while the disease control rate was 65.5% (61.3%-69.7%) with no evidence of heterogeneity (I2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.

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

Incidence and risk of regorafenib-induced hepatotoxicity. [2019] Regorafenib, an oral multi-kinase inhibitor, has been approved for the treatments of several malignancies. Unlike traditional cytotoxic chemotherapeutic agents, regorafenib therapy often induces a distinct profile of adverse events (AEs) including hepatotoxicity. Here we conducted an up-to-date meta-analysis to assess the incidence and risk of regorafenib related hepatic toxicities. PubMed and Embase database were reviewed from inception to June 2017 for relevant trials. Eligible studies include subjects with solid tumors treated with 160 mg of regorafenib daily during the first three week of each four-week cycle, and adequate safety data reporting the elevation of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. Statistical analyses were conducted to calculate the summary incidence and relative risk (RR). A total of 2,213 subjects from 14 trials were included. The incidences of regorafenib-associated all-grade and high-grade hepatotoxicity were: bilirubin elevation: 23% and 5%; AST elevation: 32% and 6%; ALT elevation: 27% and 5%; ALP elevation: 31% and 2%. Regorafenib-treated subjects had a significant increased risk of all-grade (RR = 3.10; 95% CI, 2.22-4.34) and high-grade (RR = 1.74; 95% CI, 1.09-2.80) bilirubin elevation; all-grade (RR = 1.51; 95% CI, 1.13-2.00) and high-grade (RR = 1.79; 95% CI, 1.00-3.22) AST elevation; all-grade (RR = 1.82; 95% CI, 1.25-2.64) and high-grade (RR = 3.07; 95% CI, 1.30-7.22) ALT elevation; and all-grade (RR = 2.11; 95% CI, 1.01-4.40) ALP elevation. Our results suggest that regorafenib is associated with an increased risk of hepatic toxicities. Hepatotoxicity examination at regular intervals should be advised to clinicians.

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023] There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration's (FDA) Adverse Events Reporting System (FAERS) queried reported cases of "Hepatitis B reactivation" reported with the PD-1/PD-L1 inhibitors "Pembrolizumab," "Atezolizumab," "Nivolumab," "Durvalumab," "Avelumab," and "Ipilimumab" from initial FDA approval to June 30, 2020. Disproportionality signal analysis was determined by calculating a reporting odds ratio (ROR) and 95% confidence intervals (CI). The ROR was considered significant when the lower and upper limits of the 95% CI were >1 and confirmed by the Fisher exact test (P

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] Hepatitis B reactivation can occur with cytotoxic chemotherapy in patients with hepatitis B and cancer. Reactivation can occur in a patient with chronic hepatitis, an inactive carrier, or one with resolved hepatitis. Clinical presentation may range from subclinical elevation of liver enzymes to fatal fulminant hepatic failure. Mammalian target of rapamycin inhibitors, which include everolimus, are a new generation of targeted agents that are currently approved for many cancers (since March 2009) including advanced hormone receptor positive, human epidermal growth factor receptor 2-negative breast cancer, in conjunction with exemestane (as of July 2012). We are therefore still learning the various adverse events that occur with this new class of agents. Here, we present an unfortunate case of fatal hepatitis B reactivation in a woman with metastatic breast cancer treated with everolimus and exemestane. We have detailed the controversies around hepatitis B screening prior to immunosuppressive therapy. Clinicians and patients should be aware of this rare but fatal complication prior to everolimus use, and a detailed history, screening for hepatitis B and prophylactic antiviral treatment should be considered.

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] On April 27, 2017, the U.S. Food and Drug Administration approved regorafenib for the treatment of patients with advanced hepatocellular carcinoma (HCC) who had previously been treated with sorafenib. Approval was based on the results of a single, randomized, placebo-controlled trial (RESORCE) that demonstrated an improvement in overall survival (OS). Patients were randomly allocated to receive regorafenib160 mg orally once daily or matching placebo for the first 21 days of each 28-day cycle. The trial demonstrated a significant improvement in OS (hazard ratio [HR] = 0.63; 95% confidence interval [CI], 0.50-0.79, p < .0001) with an estimated median OS of 10.6 months in the regorafenib arm and 7.8 months in the placebo arm. A statistically significant improvement in progression-free survival (PFS) based on modified RECIST for HCC [Semin Liver Dis 2010;30:52-60] (HR = 0.46; 95% CI, 0.37-0.56, p < .0001) was also demonstrated; the estimated median PFS was 3.1 and 1.5 months in the regorafenib and placebo arms, respectively. The overall response rate, based on modified RECIST for HCC, was 11% in the regorafenib arm and 4% in the placebo arm. The toxicity profile was consistent with that observed in other indications; the most clinically significant adverse reactions were palmar-plantar erythrodysesthesia, diarrhea, and hypertension. Based on the improvement in survival and acceptable toxicity, a favorable benefit-to-risk evaluation led to approval for treatment of patients with advanced HCC.