Clinical trial NCT03507452: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-04-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Incidence of DLTs (dose-limiting toxicity)
timeFrame: 6 weeks (42 days)
measure: Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs)
timeFrame: 6 months after the end of treatment
Secondary outcomes:
measure: Cmax of Thorium-227 after single dose of Cycle 1
timeFrame: From Day 1 to 43
measure: Cmax of Radium-223 after single dose of Cycle 1
timeFrame: From Day 1 to 43
measure: Cmax of Total antibody after single dose of Cycle 1
timeFrame: From Day 1 to 43
measure: AUC(0-42 days) of Radium-223 after single dose of Cycle 1
timeFrame: From Day 1 to 43
measure: AUC(0-42 days) of Total antibody after single dose of Cycle 1
timeFrame: From Day 1 to 43
measure: AUC(0-42 days) of Thorium-227 after single dose of Cycle 1
timeFrame: From Day 1 to 43
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Cancer Institute - Maryland
state: Maryland
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Helsinki
country: Finland
facility: HUS, Meilahden sairaala
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Trust (Surrey)
state: Surrey
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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.
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.