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

NCT ID: NCT03507452

Last Updated: 2023-03-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-13

Study Completion Date

2022-03-29

Brief Summary

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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

Detailed Description

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Conditions

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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)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

BAY2287411

Intervention Type DRUG

Dose Escalation part:

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

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.

Group Type EXPERIMENTAL

BAY2287411

Intervention Type DRUG

Dose Escalation part:

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

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)

Group Type EXPERIMENTAL

BAY2287411

Intervention Type DRUG

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.

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)

Group Type EXPERIMENTAL

BAY2287411

Intervention Type DRUG

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.

Dose expansion Cohort 3 (optional)

Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma

Dose / Regimen to be determined

Group Type EXPERIMENTAL

BAY2287411

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

BAY2287411

Intervention Type DRUG

Dose Escalation part:

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

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.

Group Type EXPERIMENTAL

BAY2287411

Intervention Type DRUG

Dose Escalation part:

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

Interventions

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BAY2287411

Dose Escalation part:

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

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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National Cancer Institute - Maryland

Bethesda, Maryland, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

HUS, Meilahden sairaala

Helsinki, , Finland

Site Status

Nederlands Kanker Instituut

Amsterdam, , Netherlands

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

Skånes Universitetssjukhus

Lund, , Sweden

Site Status

Royal Marsden NHS Trust (Surrey)

Sutton, Surrey, United Kingdom

Site Status

Countries

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United States Finland Netherlands Sweden United Kingdom

References

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Roy J, Jagoda EM, Basuli F, Vasalatiy O, Phelps TE, Wong K, Ton AT, Hagemann UB, Cuthbertson AS, Cole PE, Hassan R, Choyke PL, Lin FI. In Vitro and In Vivo Comparison of 3,2-HOPO Versus Deferoxamine-Based Chelation of Zirconium-89 to the Antimesothelin Antibody Anetumab. Cancer Biother Radiopharm. 2021 May;36(4):316-325. doi: 10.1089/cbr.2020.4492.

Reference Type DERIVED
PMID: 34014767 (View on PubMed)

Hagemann UB, Ellingsen C, Schuhmacher J, Kristian A, Mobergslien A, Cruciani V, Wickstroem K, Schatz CA, Kneip C, Golfier S, Smeets R, Uran S, Hennekes H, Karlsson J, Bjerke RM, Ryan OB, Mumberg D, Ziegelbauer K, Cuthbertson AS. Mesothelin-Targeted Thorium-227 Conjugate (MSLN-TTC): Preclinical Evaluation of a New Targeted Alpha Therapy for Mesothelin-Positive Cancers. Clin Cancer Res. 2019 Aug 1;25(15):4723-4734. doi: 10.1158/1078-0432.CCR-18-3476. Epub 2019 May 7.

Reference Type DERIVED
PMID: 31064781 (View on PubMed)

Related Links

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https://clinicaltrials.bayer.com/

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Other Identifiers

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2017-004052-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18795

Identifier Type: -

Identifier Source: org_study_id

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