Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04095273
Recruitment Status : Recruiting
First Posted : September 19, 2019
Last Update Posted : April 26, 2022
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE September 18, 2019
First Posted Date  ICMJE September 19, 2019
Last Update Posted Date April 26, 2022
Actual Study Start Date  ICMJE September 30, 2019
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2020)
  • Incidence of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Up to 30 days after last study intervention administration ]
  • Severity of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs) [ Time 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 [ Time Frame: Cycle 1 (21 days) ]
  • Recommended phase II dose (RP2D) of BAY1895344 [ Time Frame: Up to 24 months ]
    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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2019)
  • Incidence of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Up to 30 days after last study intervention administration ]
  • Severity of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs) [ Time 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 [ Time Frame: Cycle 1 (21 days) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2021)
  • Cmax of Elimusertib [ Time 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 [ Time Frame: Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2) ]
    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.
  • Cmax,md of Elimusertib [ Time 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 [ Time Frame: Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2) ]
    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.
  • Incidence of Complete response (CR) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Incidence of partial response (PR) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Incidence of stable disease (SD) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Incidence of progressive disease (PD) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]
  • Disease control rate (DCR) [ Time Frame: Up to 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2019)
  • Cmax of BAY1895344 [ Time Frame: Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2) ]
  • AUC(0-12) of BAY1895344 [ Time Frame: Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2) ]
    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.
  • Cmax,md of BAY1895344 [ Time 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 BAY1895344 [ Time Frame: Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2) ]
    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.
  • Incidence of Complete response (CR) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Incidence of partial response (PR) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Incidence of stable disease (SD) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Incidence of progressive disease (PD) [ Time Frame: Up to 24 months ]
    Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
  • Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]
  • Disease control rate (DCR) [ Time Frame: Up to 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: Elimusertib (BAY1895344)
    Study drugs will be administered as scheduled
  • Drug: Pembrolizumab
    Study drugs will be administered as scheduled
Study Arms  ICMJE
  • Experimental: Dose escalation of Elimusertib
    2 dose levels of Elimusertib are planned
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 1a of Elimusertib
    Participants with advanced hormone-receptor-positive, Human epidermal growth factor receptor 2 negative breast cancer (HER2-negative BC), known to be positive for Ataxia-telangiectasia mutated (ATM) loss and/or ATM deleterious alterations who have not received prior treatment with immunotherapy. Participants with known microsatellite instability-high (MSI-H) cannot be included
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 1b of Elimusertib
    Participants with advanced hormone-receptor-positive, HER2-negative BC, known to be DDR deficiency biomarker-positive (except ATM loss/mutation) who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 2a of Elimusertib
    Participants with advanced Colorectal cancer (CRC) known to be positive for ATM loss and/or ATM deleterious alterations who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 2b of Elimusertib
    Participants with advanced CRC, known to be DDR deficiency biomarker -positive (except ATM loss/mutation) who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 3 of Elimusertib
    Participants with advanced Gastric/gastroesophageal junction cancer (GC/GEJ) known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 3a of Elimusertib
    Participants with advanced GC/GEJ cancer and without DDR deficiency alterations as described above. Variants of unknown significance (VUS) of the DDR gene alterations are eligible. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 4 of Elimusertib
    Participants with advanced Non-small cell lung cancer (NSCLC) known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 4a of Elimusertib
    Participants with advanced NSCLC and without DDR deficiency alterations as described above. VUS of the DDR gene alterations are eligible. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 5 of Elimusertib
    Participants with advanced pancreatic cancer, known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 5a of Elimusertib
    Participants with advanced pancreatic cancer and without DDR deficiency alterations as described above, who have not received prior treatment with immunotherapy. VUS of the DDR gene alterations are eligible. Participants with known MSI-H cannot be included.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 6 of Elimusertib
    Participants with advanced Metastatic castration-resistant prostate cancer (mCRPC), known to be DDR deficiency biomarker positive (incl. ATM mutation) and/or positive for ATM loss who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
  • Experimental: Dose expansion cohort 6a of Elimusertib
    Participants with advanced mCRPC and without DDR deficiency alterations as described above, who have not received prior treatment with immunotherapy. VUS of the DDR gene alterations are eligible. Participants with known MSI-H cannot be included.
    Interventions:
    • Drug: Elimusertib (BAY1895344)
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 22, 2021)
125
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2019)
76
Estimated Study Completion Date  ICMJE August 29, 2024
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bayer Clinical Trials Contact +49 30 300139003 clinical-trials-contact@bayer.com
Listed Location Countries  ICMJE Germany,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04095273
Other Study ID Numbers  ICMJE 19741
Keynote 919 ( Other Identifier: Merck )
2018-003420-36 ( 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  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.

Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP