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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 : Active, not recruiting
First Posted : April 25, 2018
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE April 16, 2018
First Posted Date  ICMJE April 25, 2018
Last Update Posted Date September 17, 2021
Actual Study Start Date  ICMJE June 13, 2018
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 22, 2019)
  • Incidence of DLTs (dose-limiting toxicity) [ Time Frame: 6 weeks (42 days) ]
  • The incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs) [ Time Frame: 6 months after the end of treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2018)
Incidence of DLTs (dose-limiting toxicity) [ Time Frame: 6 weeks (42 days) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2018)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-in-human Study of BAY2287411 Injection, a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Tumors Known to Express Mesothelin
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Recurrent Epithelioid Mesothelioma
  • Serous Ovarian Cancer
  • Metastatic or Locally Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion)
Intervention  ICMJE
  • Drug: BAY2287411

    Dose Escalation part:

    A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days).

  • 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.

Study Arms  ICMJE
  • 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.

    Intervention: Drug: BAY2287411
  • 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.

    Intervention: Drug: BAY2287411
  • 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)

    Intervention: Drug: BAY2287411
  • 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)

    Intervention: Drug: BAY2287411
  • 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

    Intervention: Drug: BAY2287411
  • 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.

    Intervention: Drug: BAY2287411
  • 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.

    Intervention: Drug: BAY2287411
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 15, 2021)
36
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2018)
42
Estimated Study Completion Date  ICMJE March 21, 2022
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Finland,   Netherlands,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03507452
Other Study ID Numbers  ICMJE 18795
2017-004052-29 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP