Clinical Trials /

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

NCT03507452

Description:

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

Related Conditions:
  • Epithelioid Mesothelioma
  • Ovarian Seromucinous Carcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 18795
  • SECONDARY ID: 2017-004052-29
  • NCT ID: NCT03507452

Conditions

  • Advanced Recurrent Epithelioid Mesothelioma or Serous Ovarian Cancer
  • Metastatic or Locally Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion)

Interventions

DrugSynonymsArms
BAY2287411Dose escalation cohort a
BAY2287411Dose Expansion Cohort 1

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Dose escalation cohort aExperimentalSubjects 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.
  • BAY2287411
Dose escalation cohort bExperimentalSubjects 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.
  • BAY2287411
Dose Expansion Cohort 1ExperimentalSubjects 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)
  • BAY2287411
Dose Expansion Cohort 2ExperimentalSubjects 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)
  • BAY2287411
Dose expansion Cohort 3 (optional)ExperimentalSubjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma Dose / Regimen to be determined
  • BAY2287411

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLTs (dose-limiting toxicity)
Time Frame:6 weeks (42 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Cmax of Thorium-227 after single dose of Cycle 1
Time Frame:From Day 1 to 43
Safety Issue:
Description:
Measure:Cmax of Radium-223 after single dose of Cycle 1
Time Frame:From Day 1 to 43
Safety Issue:
Description:
Measure:Cmax of Total antibody after single dose of Cycle 1
Time Frame:From Day 1 to 43
Safety Issue:
Description:
Measure:AUC(0-42 days) of Radium-223 after single dose of Cycle 1
Time Frame:From Day 1 to 43
Safety Issue:
Description:
Measure:AUC(0-42 days) of Total antibody after single dose of Cycle 1
Time Frame:From Day 1 to 43
Safety Issue:
Description:
Measure:AUC(0-42 days) of Thorium-227 after single dose of Cycle 1
Time Frame:From Day 1 to 43
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Malignant Mesothelioma
  • Malignant Pleural Epithelioid Mesothelioma
  • Malignant Peritoneal Epithelioid Mesothelioma

Last Updated