check_circleStudy Completed

Advanced solid tumors

Study to test how well patients with advanced solid tumors respond to treatment with the Elimusertib in combination with pembrolizumab, to find the optimal dose for patients, how the drug is tolerated and the way the body absorbs, distributes and discharges the drug

Trial purpose

The purpose of the study is to test how well patients with advanced solid tumors respond to treatment with elimusertib (BAY1895344) in combination with pembrolizumab. In addition researchers want to find for patients the optimal dose of elimusertib in combination with pembrolizumab, how the drug is tolerated and the way the body absorbs, distributes and discharges the drug. The study medication, elimusertib, works by blocking a substance (ATR Kinase) which is produced by the body and is important for the growth of tumor cells. Pembrolizumab is an immunologic checkpoint blocker that promotes an immune response against the tumor.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - Participant must be ≥18 years of age inclusive, at the time of signing the informed consent.
    - Presence of the putative biomarkers of DDR deficiency in tumor and/or other tissues (dose escalation only).
    - Participants must have histologically confirmed solid tumors .
    - Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 1.
    - Adequate bone marrow function as assessed by laboratory tests to be conducted within 7 days before the first dose of study intervention.
    - Participants must have adequate kidney function, as assessed by the estimated glomerular filtration rate (eGFR) > 40 mL/min per 1.73 m*2 within 7 days before the first dose of study intervention.
    - Participants must have adequate liver function as assessed by laboratory tests to be conducted within 7 days before the first dose of study intervention.
    - Participants must have adequate coagulation, as assessed by laboratory tests as applicable, (to be conducted within 7 days before the first dose of study intervention) or be on stable anti-coagulation treatment.
    - Adequate cardiac function per institutional normal measured by echocardiography (recommended) or multigated acquisition (MUGA) scan/cardiac MRI per institutional guidelines.
    - Participants must have measurable disease (at least one measurable lesion) as per RECIST 1.1, or evaluable disease according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) classification as applicable. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  • - Ongoing infections of Common terminology criteria for adverse events (CTCAE) grade ≥2 not responding to therapy or active clinically serious infections.
    - Participants with
     -- Known human immunodeficiency virus (HIV)
     -- Active Hepatitis B infection (positive for Hepatitis B surface antigen (HBsAg)/ Hepatitis B virus (HBV) DNA).
     -- Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA results greater than the lower limits of detection of the assay).
    - Active autoimmune disease (active defined as having autoimmune disease related symptoms and detectable autoantibodies) that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
    - Diagnosis of immunodeficiency or participant is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor.
    - Pleural effusion or ascites that causes respiratory compromise (CTCAE Grade ≥ 2 dyspnea).
    - History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class >II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers, calcium channel blockers, and digoxin are permitted)
    - Uncontrolled arterial hypertension despite optimal medical management (per investigator’s opinion)
    - Moderate or severe hepatic impairment, i.e., Child-Pugh class B or C.
    - History of organ allograft transplantation
    - Evidence or history of bleeding disorder, i.e., any hemorrhage / bleeding event of CTCAE Grade > 2 within 4 weeks before the first dose of study intervention

Trial summary

Enrollment Goal
56
Trial Dates
September 2019 - April 2023
Phase
Phase 1
Could I Receive a placebo
No
Products
Elimusertib (BAY1895344)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Johns Hopkins Hospital/Health SystemBaltimore, 21287, United States
Completed
University of Texas MD Anderson Cancer CenterHouston, 77030-4000, United States
Completed
Stanford UniversityPalo Alto, 94304, United States
Completed
Ohio State UniversityColumbus, 43210, United States
Completed
Royal Marsden NHS Trust (Surrey)Sutton, SM2 5PT, United Kingdom
Completed
Yale Cancer CenterNew Haven, 06519, United States
Withdrawn
Universitätsklinikum Carl Gustav Carus DresdenDresden, 01307, Germany
Completed
Eberhard-Karls-Universität TübingenTübingen, 72076, Germany
Completed
Universitätsklinikum HeidelbergHeidelberg, 69120, Germany
Completed
Levine Cancer InstituteCharlotte, 28204-2990, United States
Completed
Weill Cornell Medical CollegeNew York, 10021, United States
Completed
Dana-Farber Cancer InstituteBoston, 02115-6084, United States
Completed
Hospital Madrid Norte SanchinarroMadrid, 28050, Spain
Completed
Fundacion Jimenez Diaz (Clinica de la Concepcion)Madrid, 28040, Spain
Completed
Freeman HospitalNewcastle, NE7 7DN, United Kingdom
Completed
Kantonsspital St. GallenSt. Gallen, 9007, Switzerland
Completed
Ospedale Regionale di Bellinzona e ValliBellinzona, 6500, Switzerland

Primary Outcome

  • Incidence of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs)
    date_rangeTime Frame:
    Up to 30 days after last study intervention administration
  • Severity of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs)
    date_rangeTime Frame:
    Up to 30 days after last study intervention administration
  • Frequency of Dose limiting toxicities (DLTs) at each dose level during dose escalation of BAY1895344
    date_rangeTime Frame:
    Cycle 1 (21 days)
  • Recommended phase II dose (RP2D) of BAY1895344
    The RP2D will be determined in dose expansion part based on multiple parameters (i.e., safety, tolerability, PK, pharmacodynamics, efficacy) and will be a dose equal to or lower than the MTD (Maximum Tolerated Dose).
    date_rangeTime Frame:
    Up to 24 months

Secondary Outcome

  • Cmax of Elimusertib
    date_rangeTime Frame:
    Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2)
  • AUC(0-12) of Elimusertib
    If the main parameters AUC(0-12) cannot be calculated reliably, it might become necessary to appoint the additional parameters AUC(0-tlast) as secondary variables.
    date_rangeTime Frame:
    Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2)
  • Cmax,md of Elimusertib
    date_rangeTime Frame:
    Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2)
  • AUC(0-12)md of Elimusertib
    If the main parameters AUC(0-12)md cannot be calculated reliably, it might become necessary to appoint the additional parameters AUC(0-tlast)md as secondary variables.
    date_rangeTime Frame:
    Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2)
  • Incidence of Complete response (CR)
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
    date_rangeTime Frame:
    Up to 24 months
  • Incidence of partial response (PR)
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
    date_rangeTime Frame:
    Up to 24 months
  • Incidence of stable disease (SD)
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
    date_rangeTime Frame:
    Up to 24 months
  • Incidence of progressive disease (PD)
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
    date_rangeTime Frame:
    Up to 24 months
  • Objective Response Rate (ORR)
    date_rangeTime Frame:
    Up to 24 months
  • Disease control rate (DCR)
    date_rangeTime Frame:
    Up to 24 months

Trial design

A multicenter, non-randomized, open-label Phase 1b study to determine the maximum tolerated and recommended Phase 2 dose of the ATR inhibitor elimusertib in combination with pembrolizumab and to characterize its safety, tolerability, pharmacokinetics and preliminary anti-tumor activity in participants with advanced solid tumors
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Sequential Assignment
Trial Arms
13