First-in-human Study of BAY2287411 Injection, a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Tumors Known to Express Mesothelin
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| ClinicalTrials.gov Identifier: NCT03507452 |
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Recruitment Status :
Completed
First Posted : April 25, 2018
Last Update Posted : March 20, 2023
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma Advanced Recurrent Serous Ovarian Cancer Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion, Not Initiated) | Drug: BAY2287411 | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 36 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, BAY2287411 Injection, in Patients With Solid Tumors Known to Express Mesothelin |
| Actual Study Start Date : | June 13, 2018 |
| Actual Primary Completion Date : | September 29, 2021 |
| Actual Study Completion Date : | March 29, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose escalation cohort a
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. |
Drug: BAY2287411
Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days). |
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Experimental: Dose escalation cohort b
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. |
Drug: BAY2287411
Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days). |
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Experimental: Dose Expansion Cohort 1
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) |
Drug: BAY2287411
Dose Expansion part: The selection of the dose level(s) /regimen(s) to be evaluated will be based on the overall benefit / risk and PK profile observed in the dose escalation. |
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Experimental: Dose Expansion Cohort 2
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) |
Drug: BAY2287411
Dose Expansion part: The selection of the dose level(s) /regimen(s) to be evaluated will be based on the overall benefit / risk and PK profile observed in the dose escalation. |
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Experimental: Dose expansion Cohort 3 (optional)
Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma Dose / Regimen to be determined |
Drug: BAY2287411
Dose Expansion part: The selection of the dose level(s) /regimen(s) to be evaluated will be based on the overall benefit / risk and PK profile observed in the dose escalation. |
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Experimental: Dose escalation cohort c
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. |
Drug: BAY2287411
Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days). |
|
Experimental: Dose escalation cohort d
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. |
Drug: BAY2287411
Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days). |
- Incidence of DLTs (dose-limiting toxicity) [ Time Frame: 6 weeks (42 days) ]
- Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs) [ Time Frame: 6 months after the end of treatment ]
- Cmax of Thorium-227 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
- Cmax of Radium-223 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
- Cmax of Total antibody after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
- AUC(0-42 days) of Radium-223 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
- AUC(0-42 days) of Total antibody after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
- AUC(0-42 days) of Thorium-227 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03507452
| United States, Maryland | |
| National Cancer Institute - Maryland | |
| Bethesda, Maryland, United States, 20892 | |
| United States, Texas | |
| University of Texas MD Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Finland | |
| HUS, Meilahden sairaala | |
| Helsinki, Finland, 00290 | |
| Netherlands | |
| Nederlands Kanker Instituut | |
| Amsterdam, Netherlands, 1066 CX | |
| Universitair Medisch Centrum Groningen | |
| Groningen, Netherlands, 9713 GZ | |
| Sweden | |
| Skånes Universitetssjukhus | |
| Lund, Sweden, 221 85 | |
| United Kingdom | |
| Royal Marsden NHS Trust (Surrey) | |
| Sutton, Surrey, United Kingdom, SM2 5PT | |
| Study Director: | Bayer Study Director | Bayer |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT03507452 |
| Other Study ID Numbers: |
18795 2017-004052-29 ( EudraCT Number ) |
| First Posted: | April 25, 2018 Key Record Dates |
| Last Update Posted: | March 20, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Malignant Mesothelioma Malignant Pleural Epithelioid Mesothelioma Malignant Peritoneal Epithelioid Mesothelioma |
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Mesothelioma Mesothelioma, Malignant Recurrence Disease Attributes Pathologic Processes Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms by Site Adenoma |
Neoplasms, Mesothelial Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Pleural Neoplasms Lung Diseases Respiratory Tract Diseases BAY 2287411 Radiopharmaceuticals Molecular Mechanisms of Pharmacological Action |