check_circleStudy Completed

Metastatic castration resistant prostate cancer (mCRPC)

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

Trial purpose

The study medication (BAY 2315497 Injection) is a thorium-227 labeled immuno-conjugate, specific for the prostate-specific membrane antigen (PSMA), which will be evaluated in patients with metastatic castration resistant prostate cancer. In this study, this investigational medication will be administered to patients for the first time. The primary objective of the study is to define the safety and tolerability profile and Maximal Tolerated Dose (MTD) of BAY2315497 Injection alone, or in combination with darolutamide. The secondary objectives are to determine the recommended dose for further clinical development of BAY2315497 Injection alone, or in combination with darolutamide and to investigate how the study drug is distributed and cleared from the body.

Key Participants Requirements

Sex

Male

Age

18 - N/A
  • - 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.
  • - 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

Trial summary

Enrollment Goal info
63
Trial Dates info
December 2018 - October 2024
Phase info
Phase 1
Could I Receive a placebo info
No
Products info
BAY2315497
Accepts Healthy Volunteer info
No

Where to participate

StatusInstitutionLocation
Completed
Royal Marsden NHS Trust (Surrey)Sutton, SM2 5PT, United Kingdom
Completed
HUS, Meilahden sairaalaHelsinki, FIN-00260, Finland
Withdrawn
Skånes UniversitetssjukhusLund, 221 85, Sweden
Completed
Memorial Sloan-Kettering Cancer CenterNew York, 10065, United States
Completed
Tulane Medical CenterNew Orleans, 70112, United States
Completed
GU Research Network, LLCOmaha, 68130, United States
Withdrawn
Washington University School of MedicineSt. Louis, 63110, United States
Withdrawn
Klinikum rechts der IsarMünchen, 81675, Germany
Withdrawn
Erasmus Medisch CentrumROTTERDAM, 3015 CE, Netherlands

Primary Outcomeinfo

  • Maximum tolerated dose (MTD) of BAY2315497 injection
    The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.
    date_rangeTime Frame:
    Cycle 1 (42 days)
  • Maximum tolerated dose (MTD) of BAY2315497 injection in combination with darolutamide
    The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.
    date_rangeTime Frame:
    Cycle 1 (42 days)

Secondary Outcomeinfo

  • Recommended dose for further clinical development of BAY2315497 injection
    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.
    date_rangeTime 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)
  • Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium of BAY2315497 Injection
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • Cmax of radium of BAY2315497 Injection
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • AUC(0-42) days of radium of BAY2315497 Injection
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • Cmax of total antibody of BAY2315497 Injection
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • AUC(0-42) days of total antibody of BAY2315497 Injection
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • Recommended dose for further clinical development of BAY2315497 injection in combination with darolutamide
    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.
    date_rangeTime 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)
  • Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection in combination with darolutamide
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • 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
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • Cmax of radium of BAY2315497 Injection in combination with darolutamide
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • AUC(0-42) days of radium of BAY2315497 Injection in combination with darolutamide
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • Cmax of total antibody of BAY2315497 Injection in combination with darolutamide
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)
  • AUC(0-42) days of total antibody of BAY2315497 Injection in combination with darolutamide
    date_rangeTime Frame:
    Cycle 1 (From day 1 to 43)

Trial design

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
Trial Type info
Interventional
Intervention Type info
Drug
Trial Purpose info
Treatment
Allocation info
Non-randomized
Blinding info
N/A
Assignment info
Sequential Assignment
Trial Arms info
4