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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT03507452

Collaborator

(none)

Enrollment

Locations

Arms

45.5

Actual Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Recurrent Epithelioid Mesothelioma Serous Ovarian Cancer Metastatic or Locally Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion)	Drug: BAY2287411 Drug: BAY2287411	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 13, 2018

Actual Primary Completion Date :

Sep 29, 2021

Actual Study Completion Date :

Mar 29, 2022

Arms and Interventions

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 mg.	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 within the range of 10 - 50 mg.	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 - 150 mg mg.	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 - 400 mg.	Drug: BAY2287411 Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days).

Outcome Measures

Primary Outcome Measures

Incidence of DLTs (dose-limiting toxicity) [6 weeks (42 days)]
The incidence of 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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Institute	Bethesda	Maryland	United States	20892
2	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
3	HUS, Meilahden sairaala	Helsinki		Finland	00290
4	Nederlands Kanker Instituut	Amsterdam		Netherlands	1066 CX
5	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 GZ
6	Skånes Universitetssjukhus	Lund		Sweden	221 85
7	Royal Marsden NHS Trust (Surrey)	Sutton	Surrey	United Kingdom	SM2 5PT