First-in-human Study Of BAY2287411 Injection, A Thorium-227 Labeled Antibody-chelator Conjugate, In Patients With Tumors Known To Express Mesothelin

Study Overview

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

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

N/A

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
DRUG: BAY2287411

18795
2017-004052-29 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-04-16	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-03-17
First Submitted that Met QC Criteria 2018-04-16	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-03-20
First Posted (ACTUAL) 2018-04-25	Results First Posted N/A	Last Verified 2023-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/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 m	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	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.
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 -	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 -	DRUG: BAY2287411 Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days).

Primary Outcome Measures	Measure Description	Time Frame
Incidence of DLTs (dose-limiting toxicity)		6 weeks (42 days)
Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs)		6 months after the end of treatment

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Bayer Study Director, Bayer

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
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.

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