First-in-human Study of BAY2287411 Injection, a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Tumors Known to Express Mesothelin

Phase 1

Completed

• Conditions: Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion, Not Initiated); Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma; Advanced Recurrent Serous Ovarian Cancer; Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma
• Interventions: Drug: BAY2287411

• Registration Number: NCT03507452
• Lead Sponsor: Bayer

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

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-04-16
• Study First Submitted QC: 2018-04-16
• Study First Posted: 2018-04-25
• Study Start: 2018-06-13
• Primary Completion: 2021-09-29
• Study Completion: 2022-03-29
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-17
• Last Update Posted: 2023-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation cohort a	BAY2287411	Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 mg.
Dose Expansion Cohort 2	BAY2287411	Subjects with advanced recurrent epithelioid mesothelioma or serous ovarian cancer, who have exhausted available therapeutic options Dose / Regimen 2 (to be determined after completion of the dose escalation)
Dose escalation cohort b	BAY2287411	Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with a total antibody dose within the range of 10 - 50 mg.
Dose Expansion Cohort 1	BAY2287411	Subjects with advanced recurrent epithelioid mesothelioma or serous ovarian cancer, who have exhausted available therapeutic options Dose / Regimen 1 (to be determined after completion of the dose escalation)
Dose escalation cohort c	BAY2287411	Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 - 150 mg mg.
Dose expansion Cohort 3 (optional)	BAY2287411	Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma Dose / Regimen to be determined
Dose escalation cohort d	BAY2287411	Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 - 400 mg.

Primary Outcome Measures

Name	Time	Method
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
Incidence of DLTs (dose-limiting toxicity)	6 weeks (42 days)

Secondary Outcome Measures

Name	Time	Method
Cmax of Radium-223 after single dose of Cycle 1	From Day 1 to 43
Cmax of Total antibody 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
Cmax 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
AUC(0-42 days) of Radium-223 after single dose of Cycle 1	From Day 1 to 43

Trial Locations

Locations (7)

HUS, Meilahden sairaala; 🇫🇮 Helsinki, Finland

Nederlands Kanker Instituut; 🇳🇱 Amsterdam, Netherlands

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

Skånes Universitetssjukhus; 🇸🇪 Lund, Sweden

Royal Marsden NHS Trust (Surrey); 🇬🇧 Sutton, Surrey, United Kingdom

National Cancer Institute - Maryland; 🇺🇸 Bethesda, Maryland, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States