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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
Recruitment Status : Recruiting
First Posted : April 25, 2018
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Advanced Recurrent Epithelioid Mesothelioma Serous Ovarian Cancer Metastatic or Locally Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion) Drug: BAY2287411 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 228 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
Estimated Primary Completion Date : June 6, 2022
Estimated Study Completion Date : February 20, 2023


Arm Intervention/treatment
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).


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).


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.


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.


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.





Primary Outcome Measures :
  1. Incidence of DLTs (dose-limiting toxicity) [ Time Frame: 6 weeks (42 days) ]

Secondary Outcome Measures :
  1. Cmax of Thorium-227 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
  2. Cmax of Radium-223 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
  3. Cmax of Total antibody after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
  4. AUC(0-42 days) of Radium-223 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
  5. AUC(0-42 days) of Total antibody after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
  6. AUC(0-42 days) of Thorium-227 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Contacts
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Contact: Bayer Clinical Trials Contact (+) 1-888-8422937 clinical-trials-contact@bayer.com

Locations
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United States, Maryland
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Finland
HUS, Meilahden sairaala Recruiting
Helsinki, Finland, 00290
Netherlands
Nederlands Kanker Instituut Recruiting
Amsterdam, Netherlands, 1066 CX
Universitair Medisch Centrum Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Sweden
Skånes Universitetssjukhus Recruiting
Lund, Sweden, 221 85
United Kingdom
Royal Marsden NHS Trust (Surrey) Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03507452     History of Changes
Other Study ID Numbers: 18795
2017-004052-29 ( EudraCT Number )
First Posted: April 25, 2018    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Malignant Mesothelioma
Malignant Pleural Epithelioid Mesothelioma
Malignant Peritoneal Epithelioid Mesothelioma
Additional relevant MeSH terms:
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Adenocarcinoma
Mesothelioma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenoma
Neoplasms, Mesothelial
Antibodies
Immunoglobulins
Chelating Agents
Immunologic Factors
Physiological Effects of Drugs
Sequestering Agents
Molecular Mechanisms of Pharmacological Action