Advanced Recurrent Malignant Pleural Epithelioid MesotheliomaPhase 1NCT03507452
First-in-human Study of BAY2287411 Injection, a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Tumors Known to Express Mesothelin
A Phase 1 study testing BAY2287411 in people with Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma and Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma, run by Bayer at 7 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma, Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma, Advanced Recurrent Serous Ovarian Cancer
- What is being tested?
- BAY2287411
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 13 Jun 2018to 29 Mar 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
United States2 sites
National Cancer Institute - Maryland
Bethesda, Maryland, 20892
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Netherlands2 sites
Nederlands Kanker Instituut
Amsterdam, 1066 CX
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
United Kingdom1 site
Royal Marsden NHS Trust (Surrey)
Sutton, Surrey, SM2 5PT
About this study
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
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
- 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)
- Being tested
- BAY2287411
- Keywords
- Malignant Mesothelioma, Malignant Pleural Epithelioid Mesothelioma, Malignant Peritoneal Epithelioid Mesothelioma
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY2287411Drug
Dose Escalation part:
A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days).
BAY2287411Drug
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 group | Role | What they receive |
|---|---|---|
| Dose escalation cohort a | Experimental | 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. Receives: Drug: BAY2287411 |
| Dose escalation cohort b | Experimental | 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. Receives: Drug: BAY2287411 |
| Dose Expansion Cohort 1 | Experimental | 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) Receives: Drug: BAY2287411 |
| Dose Expansion Cohort 2 | Experimental | 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) Receives: Drug: BAY2287411 |
| Dose expansion Cohort 3 (optional) | Experimental | Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma
Dose / Regimen to be determined Receives: Drug: BAY2287411 |
| Dose escalation cohort c | Experimental | 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. Receives: Drug: BAY2287411 |
| Dose escalation cohort d | Experimental | 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. Receives: Drug: BAY2287411 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs (dose-limiting toxicity)
Measured: 6 weeks (42 days)
Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs)
Measured: 6 months after the end of treatment
Secondary outcomes (6)
Cmax of Thorium-227 after single dose of Cycle 1
Measured: From Day 1 to 43
Cmax of Radium-223 after single dose of Cycle 1
Measured: From Day 1 to 43
Cmax of Total antibody after single dose of Cycle 1
Measured: From Day 1 to 43
AUC(0-42 days) of Radium-223 after single dose of Cycle 1
Measured: From Day 1 to 43
AUC(0-42 days) of Total antibody after single dose of Cycle 1
Measured: From Day 1 to 43
AUC(0-42 days) of Thorium-227 after single dose of Cycle 1
Measured: From Day 1 to 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2018
- Study start13 Jun 2018
- Primary completion29 Sep 2021
- Study completion29 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Recurrent Malignant Pleural Epithelioid MesotheliomaStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03507452
- Sponsor's protocol ID
- 18795
- Other IDs
- 2017-004052-29, 2017
- Status last verified
- Mar 2023
- First submitted
- 16 Apr 2018
- Last updated
- 20 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
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.
PubMed 34014767Hagemann 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.
PubMed 31064781
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03507452
- Acronym / sponsor ID
- 18795
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2018 (actual)
- Primary completion
- 29 Sep 2021 (actual)
- Study completion
- 29 Mar 2022 (actual)
- First posted
- 25 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Dose escalation cohort a | Experimental | Drug: BAY2287411Subjects 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. |
| Dose escalation cohort b | Experimental | Drug: BAY2287411Subjects 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. |
| Dose Expansion Cohort 1 | Experimental | Drug: BAY2287411Subjects 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) |
| Dose Expansion Cohort 2 | Experimental | Drug: BAY2287411Subjects 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) |
| Dose expansion Cohort 3 (optional) | Experimental | Drug: BAY2287411Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma Dose / Regimen to be determined |
| Dose escalation cohort c | Experimental | Drug: BAY2287411Subjects 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. |
| Dose escalation cohort d | Experimental | Drug: BAY2287411Subjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAY2287411Dose Escalation part: A single dose will be administered intravenously on Day 1 of each cycle lasting 6 weeks (42 days). | Drug | Dose escalation cohort a, Dose escalation cohort b, Dose escalation cohort c, Dose escalation cohort d |
| BAY2287411Dose 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. | Drug | Dose Expansion Cohort 1, Dose Expansion Cohort 2, Dose expansion Cohort 3 (optional) |
Primary outcome
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
6 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2023.
- Derived from this study: PubMed 34014767Roy 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.
- Derived from this study: PubMed 31064781Hagemann 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.
- Individual participant dataSharing planned: No. 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BAY2287411 in people with Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma and Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma, run by Bayer at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Netherlands, Finland, Sweden, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of DLTs (dose-limiting toxicity) (time frame: 6 weeks (42 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03507452, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2023.