Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion, Not Initiated), Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma, Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma, Advanced Recurrent Serous Ovarian Cancer
Conditions
Keywords
Malignant Mesothelioma, Malignant Pleural Epithelioid Mesothelioma, Malignant Peritoneal Epithelioid Mesothelioma
Brief summary
The purpose of this study is to evaluate, in patients with tumors known to express the protein mesothelin, the following properties of BAY2287411 injection: * safety (to identify, assess, minimize, and appropriately manage the risks associated to the study drug) * tolerability (the degree to which side effects can be tolerated by your body) * maximum tolerated dose * pharmacokinetics (the effect of your body on the study drug) * anti-tumor activity * recommended dose for further clinical development
Interventions
DRUGBAY2287411
Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days).
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Male or female subjects ≥ 18 years of age * ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1 * Patients with advanced malignant epithelioid mesothelioma or advanced recurrent serous ovarian cancer, who have exhausted available therapeutic options; in addition, in the dose expansion part of the study, patients with metastatic pancreatic adenocarcinoma, who have exhausted available therapeutic options * Availability of fresh or archival tumor tissue samples * Adequate bone marrow, liver and renal function, as assessed by pre-defined laboratory requirements (within 28 days before start of study drug treatment) * A negative serum pregnancy test in women of childbearing potential (WOCBP) performed within 7 days before the start of study drug administration. Women and men of reproductive potential must agree to use highly effective methods of contraception, when sexually active.
Exclusion criteria
* Impaired cardiac function, clinically significant cardiac disease or cardiac arrhythmias * Pericarditis (any CTCAE grade) or pericardial effusion (CTCAE Grade ≥ 2) * Left Ventricular Ejection Fraction (LVEF) \< 50% (as measured at screening by echocardiogram). * History of anaphylactic reactions to monoclonal antibody therapy * History of Myelodysplastic syndrome (MDS)/treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML * Infections of CTCAE (Common Terminology Criteria for Adverse Events) version 5.0 Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade \>2; known human immunodeficiency virus (HIV) infection; active hepatitis B virus (HBV) or hepatitis C virus (HCV)infection requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator's discretion provided that the disease is stable and sufficiently controlled under treatment * Known brain, spinal or meningeal metastases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of DLTs (dose-limiting toxicity) | 6 weeks (42 days) |
| Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs) | 6 months after the end of treatment |
Secondary
| Measure | Time frame |
|---|---|
| Cmax of Total antibody after single dose of Cycle 1 | From Day 1 to 43 |
| AUC(0-42 days) of Radium-223 after single dose of Cycle 1 | From Day 1 to 43 |
| Cmax of Thorium-227 after single dose of Cycle 1 | From Day 1 to 43 |
| AUC(0-42 days) of Thorium-227 after single dose of Cycle 1 | From Day 1 to 43 |
| AUC(0-42 days) of Total antibody after single dose of Cycle 1 | From Day 1 to 43 |
| Cmax of Radium-223 after single dose of Cycle 1 | From Day 1 to 43 |
Countries
Finland, Netherlands, Sweden, United Kingdom, United States
Outcome results
None listed