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

• ClinicalTrials.gov Identifier: NCT03507452
• Recruitment Status: Completed
• First Posted: April 25, 2018
• Last Update Posted: March 20, 2023
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: April 16, 2018
• First Posted Date: April 25, 2018
• Last Update Posted Date: March 20, 2023
• Actual Study Start Date: June 13, 2018
• Actual Primary Completion Date: September 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 17, 2023)

• Incidence of DLTs (dose-limiting toxicity) [ Time Frame: 6 weeks (42 days) ]
• 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 ]

• Original Primary Outcome Measures (submitted: April 16, 2018): Incidence of DLTs (dose-limiting toxicity) [ Time Frame: 6 weeks (42 days) ]

Current Secondary Outcome Measures (submitted: September 26, 2018)

• Cmax of Thorium-227 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
• Cmax of Radium-223 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
• Cmax of Total antibody after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
• AUC(0-42 days) of Radium-223 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
• AUC(0-42 days) of Total antibody after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]
• AUC(0-42 days) of Thorium-227 after single dose of Cycle 1 [ Time Frame: From Day 1 to 43 ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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)

Intervention

• Drug: BAY2287411

  Dose Escalation part:

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

• 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.

Study Arms

• 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.

  Intervention: Drug: BAY2287411
• 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.

  Intervention: Drug: BAY2287411
• 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)

  Intervention: Drug: BAY2287411
• 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)

  Intervention: Drug: BAY2287411
• 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

  Intervention: Drug: BAY2287411
• 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.

  Intervention: Drug: BAY2287411
• 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.

  Intervention: Drug: BAY2287411

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 15, 2021): 36
• Original Estimated Enrollment (submitted: April 16, 2018): 42
• Actual Study Completion Date: March 29, 2022
• Actual Primary Completion Date: September 29, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland, Netherlands, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03507452
• Other Study ID Numbers: 18795; 2017-004052-29 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

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.

• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: March 2023