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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

Primary Purpose

Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma, Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma, Advanced Recurrent Serous Ovarian Cancer

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BAY2287411

About this trial

This is an interventional treatment trial for Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma focused on measuring Malignant Mesothelioma, Malignant Pleural Epithelioid Mesothelioma, Malignant Peritoneal Epithelioid Mesothelioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

National Cancer Institute - Maryland
University of Texas MD Anderson Cancer Center
HUS, Meilahden sairaala
Nederlands Kanker Instituut
Universitair Medisch Centrum Groningen
Skånes Universitetssjukhus
Royal Marsden NHS Trust (Surrey)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Dose escalation cohort a

Dose escalation cohort b

Dose Expansion Cohort 1

Dose Expansion Cohort 2

Dose expansion Cohort 3 (optional)

Dose escalation cohort c

Dose escalation cohort d

Arm Description

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.

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)

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)

Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma Dose / Regimen to be determined

Outcomes

Primary Outcome Measures

Incidence of DLTs (dose-limiting toxicity)

Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs)

Secondary Outcome Measures

Cmax of Thorium-227 after single dose of Cycle 1

Cmax of Radium-223 after single dose of Cycle 1

Cmax of Total antibody after single dose of Cycle 1

AUC(0-42 days) of Radium-223 after single dose of Cycle 1

AUC(0-42 days) of Total antibody after single dose of Cycle 1

AUC(0-42 days) of Thorium-227 after single dose of Cycle 1

Full Information

NCT ID

NCT03507452

First Posted

April 16, 2018

Last Updated

March 17, 2023

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT03507452

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

June 13, 2018 (Actual)

Primary Completion Date

September 29, 2021 (Actual)

Study Completion Date

March 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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)

Keywords

Malignant Mesothelioma, Malignant Pleural Epithelioid Mesothelioma, Malignant Peritoneal Epithelioid Mesothelioma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose escalation cohort a

Arm Type

Experimental

Arm Description

Arm Title

Dose escalation cohort b

Arm Type

Experimental

Arm Description

Arm Title

Dose Expansion Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Dose Expansion Cohort 2

Arm Type

Experimental

Arm Description

Arm Title

Dose expansion Cohort 3 (optional)

Arm Type

Experimental

Arm Description

Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma Dose / Regimen to be determined

Arm Title

Dose escalation cohort c

Arm Type

Experimental

Arm Description

Arm Title

Dose escalation cohort d

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

BAY2287411

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

BAY2287411

Intervention Description

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 Measure Information:

Title

Incidence of DLTs (dose-limiting toxicity)

Time Frame

6 weeks (42 days)

Title

Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs)

Time Frame

6 months after the end of treatment

Secondary Outcome Measure Information:

Title

Cmax of Thorium-227 after single dose of Cycle 1

Time Frame

From Day 1 to 43

Title

Cmax of Radium-223 after single dose of Cycle 1

Time Frame

From Day 1 to 43

Title

Cmax of Total antibody after single dose of Cycle 1

Time Frame

From Day 1 to 43

Title

AUC(0-42 days) of Radium-223 after single dose of Cycle 1

Time Frame

From Day 1 to 43

Title

AUC(0-42 days) of Total antibody after single dose of Cycle 1

Time Frame

From Day 1 to 43

Title

AUC(0-42 days) of Thorium-227 after single dose of Cycle 1

Time Frame

From Day 1 to 43

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

Facility Name

National Cancer Institute - Maryland

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

HUS, Meilahden sairaala

City

Helsinki

ZIP/Postal Code

00290

Country

Finland

Facility Name

Nederlands Kanker Instituut

City

Amsterdam

ZIP/Postal Code

1066 CX

Country

Netherlands

Facility Name

Universitair Medisch Centrum Groningen

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Skånes Universitetssjukhus

City

Lund

ZIP/Postal Code

221 85

Country

Sweden

Facility Name

Royal Marsden NHS Trust (Surrey)

City

Sutton

State/Province

Surrey

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Citations:

PubMed Identifier

34014767

Citation

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.

Results Reference

derived

PubMed Identifier

31064781

Citation

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.

Results Reference

derived

Links:

URL

https://clinicaltrials.bayer.com/

Description

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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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