- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03724747
Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer
A Phase 1, 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, BAY 2315497 Injection Alone, and in Combination With Darolutamide (BAY 1841788), in Patients With Metastatic Castration Resistant Prostate Cancer
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Helsinki, Finland, 00290
- HUS, Meilahden sairaala
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Surrey
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Sutton, Surrey, United Kingdom, SM2 5PT
- Royal Marsden NHS Trust (Surrey)
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Louisiana
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New Orleans, Louisiana, United States, 70112
- Tulane Medical Center
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Nebraska
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Omaha, Nebraska, United States, 68130
- GU Research Network, LLC
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New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
- Ability to understand and sign an approved informed consent form.
- Male adult patients (≥ 18 years of age).
- ECOG PS of 0 or 1.
- Life expectancy ≥ 6 months.
- Histological, pathological and/or cytological confirmation of adenocarcinoma of the prostate without small cell or neuroendocrine features.
- Previous treatment with at least one novel androgen axis drug (NAAD) (e.g. enzalutamide and/or abiraterone).
- Patients must have prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
- Previous treatment with at least 1, but no more than 2 previous - taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient has received only 1 taxane regimen, he is eligible, if refuses to receive a second taxane regimen, or is considered unsuitable to receive a second taxane regimen (e.g. intolerance).
- Documented progression of mCRPC, as defined according to the Prostate Cancer Working Group 3 (PCWG3) guidelines.
Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements, to be conducted within 14 days before start of study drug administration:
- Hemoglobin > 9.0 g/dL
- Absolute neutrophil count (ANC) > 1500/mm3
- White blood cell (WBC) count > 3000/mL
- Platelet count > 100,000 /mm*3
- Total bilirubin < 1,5 x upper limit of normal (ULN) (except if confirmed history of Gilbert's disease)
- ALT and AST ≤ 2.5 x ULN
- Serum creatinine ≤ 1.5 X ULN and glomerular filtration rate (GFR ≥ 45 mL/min/1.73 m2, according to the MDRD (Modified Diet in Renal Disease) abbreviated formula.
- Patients with partners of childbearing potential must be willing to use highly effective methods of birth control for the time period between the first administration of BAY 2315497 Injection to at least 6 months after the last administration of the study drug.
- In the darolutamide BAY2315497 Injection combination escalation arm, patients at sites performing the PSMA and FDG PET/CTs should be able to tolerate the 3 radiotracer injections and the 3 whole body PET/CT scans.
Exclusion Criteria
- Diffuse bone or bone-marrow involvement (i.e. "superscan").
- Spinal cord compression or known brain metastases.
- Known incompatibility to CT/MRI, bone scan or uncontrolled pain, which results in patient's lack of compliance with the CT/MRI and bone scan required for PCWG3 tumor assessment.
- Clinically significant heart disease, as evidenced by myocardial infarction, arterial thrombotic events in the past 6 months, severe or unstable angina, or uncontrolled cardiovascular history.
- Patients known to be affected by genetic defects linked to radiation Hypersensitivity.
- Known history of myelodysplastic syndrome (MDS) / leukemia or with features suggestive of MDS/AML at any time point.
- Concurrent or active cancer within the last 2 years with a distinct primary site or histology from the cancer being evaluated in this study, with the exception of cancer types with less than 30% likelihood of recurrence.
- Known allergies, hypersensitivity, or intolerance to the study drug including excipients, or to contrast agents used in the diagnostic or exploratory imaging procedures required per protocol.
- Any infection of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 Grade ≥ 2.
- Known human immunodeficiency virus (HIV) infection.
- Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
- Serious, non-healing wound, ulcer, or bone fracture.
- Any systemic anti-neoplastic therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies], PARP inhibitors) within at least 30 days prior to day of randomization (except for Luteinizing Hormone-releasing Hormone [LHRH] or Gonadotropin-releasing Hormone [GnRH]).
- Previous high-dose chemotherapy, needing hemopoietic stem cell rescue, is prohibited.
- Prior major surgery (excluding prostatic biopsies) must be at least 12 weeks prior to study entry.
- Previous treatment with therapeutic PSMA-targeted agents.
- Previous treatment with radium-223 dichloride or other radiopharmaceuticals, including but not limited to strontium-89 or samarium-153.
- Prior definitive radiotherapy completed less than 6 weeks before start of the study drug administration
- Inability to swallow oral medications
- A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of darolutamide
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: BAY2315497 dose escalation
The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme.
The total antibody dose of 50 mg will be evaluated first; on the basis of emerging clinical data, doses within the range of 20-100 mg may be investigated.
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BAY 2315497 Injection comprises 3 components: the PSMA-specific monoclonal antibody (mAb), the mAb-chelator conjugate, and the thorium-227 labeled mAb-chelator conjugate.
BAY 2315497 Injection will be administered on Day 1 of each treatment cycle.
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Experimental: BAY2315497 dose escalation in combination with darolutamide
The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme.
In addition, Darolutamide oral dosing at the approved dose of twice daily 600 mg will be initiated 14 days prior to the first BAY2315497 Injection dose on Day 1 of the first cycle.
Daily darolutamide dosing will continue throughout the entire BAY2315497 Injection treatment period until withdrawal criteria from study treatment period are met.
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BAY 2315497 Injection comprises 3 components: the PSMA-specific monoclonal antibody (mAb), the mAb-chelator conjugate, and the thorium-227 labeled mAb-chelator conjugate.
BAY 2315497 Injection will be administered on Day 1 of each treatment cycle.
600 mg (2 X 300 mg tablets), twice daily with food, equivalent to a total daily dose of 1200 mg.
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Experimental: BAY2315497 dose expansion:Dose regimen 1
The thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY2315497 Injection, observed in the course of the dose escalation.
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BAY 2315497 Injection comprises 3 components: the PSMA-specific monoclonal antibody (mAb), the mAb-chelator conjugate, and the thorium-227 labeled mAb-chelator conjugate.
BAY 2315497 Injection will be administered on Day 1 of each treatment cycle.
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Experimental: BAY2315497 dose expansion:Dose regimen 2
The thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY2315497 Injection, observed in the course of the dose escalation.
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BAY 2315497 Injection comprises 3 components: the PSMA-specific monoclonal antibody (mAb), the mAb-chelator conjugate, and the thorium-227 labeled mAb-chelator conjugate.
BAY 2315497 Injection will be administered on Day 1 of each treatment cycle.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Maximum tolerated dose (MTD) of BAY2315497 injection
Time Frame: Cycle 1 (42 days)
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The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.
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Cycle 1 (42 days)
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Maximum tolerated dose (MTD) of BAY2315497 injection in combination with darolutamide
Time Frame: Cycle 1 (42 days)
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The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.
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Cycle 1 (42 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Recommended dose for further clinical development of BAY2315497 injection
Time Frame: Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented)
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The dose / regimen recommended for further clinical development will be defined after evaluation of the safety, PK and overall clinical data, collected in cycle 1 and subsequent cycles, in the dose escalation and dose expansion parts of the study.
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Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented)
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Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium of BAY2315497 Injection
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Cmax of radium of BAY2315497 Injection
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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AUC(0-42) days of radium of BAY2315497 Injection
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Cmax of total antibody of BAY2315497 Injection
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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AUC(0-42) days of total antibody of BAY2315497 Injection
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Recommended dose for further clinical development of BAY2315497 injection in combination with darolutamide
Time Frame: Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented)
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The dose / regimen recommended for further clinical development will be defined after evaluation of the safety, PK and overall clinical data, collected in cycle 1 and subsequent cycles, in the dose escalation and dose expansion parts of the study.
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Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented)
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Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection in combination with darolutamide
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium of BAY2315497 Injection in combination with darolutamide
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Cmax of radium of BAY2315497 Injection in combination with darolutamide
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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AUC(0-42) days of radium of BAY2315497 Injection in combination with darolutamide
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Cmax of total antibody of BAY2315497 Injection in combination with darolutamide
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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AUC(0-42) days of total antibody of BAY2315497 Injection in combination with darolutamide
Time Frame: Cycle 1 (From day 1 to 43)
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Cycle 1 (From day 1 to 43)
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 19445
- 2018-001490-25 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD 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.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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