Clinical Trials /

Study to Test How Well Patients With Advanced Solid Tumors Respond to Treatment With the ATR Inhibitor BAY1895344 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

NCT04095273

Description:

The purpose of the study is to test how well patients with advanced solid tumors respond to treatment with BAY1895344 in combination with pembrolizumab. In addition researchers want to find for patients the optimal dose of BAY1895344 in combination with pembrolizumab, how the drug is tolerated and the way the body absorbs, distributes and discharges the drug. The study medication, BAY1895344, 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.

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Gastric Carcinoma
  • Hepatocellular Carcinoma
  • Kidney Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
  • Prostate Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Test How Well Patients With Advanced Solid Tumors Respond to Treatment With the ATR Inhibitor BAY1895344 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: A Multicenter, Non-randomized, Open-label Phase 1b Study to Determine the Maximum Tolerated and Recommended Phase 2 Dose of the ATR Inhibitor BAY1895344 in Combination With Pembrolizumab and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 19741
  • SECONDARY ID: 2018-003420-36
  • NCT ID: NCT04095273

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
BAY1895344Dose escalation of BAY1895344
PembrolizumabDose escalation of BAY1895344

Purpose

The purpose of the study is to test how well patients with advanced solid tumors respond to treatment with BAY1895344 in combination with pembrolizumab. In addition researchers want to find for patients the optimal dose of BAY1895344 in combination with pembrolizumab, how the drug is tolerated and the way the body absorbs, distributes and discharges the drug. The study medication, BAY1895344, works by blocking a substance (ATR Kinase) which 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.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of BAY1895344Experimental2 dose levels of BAY1895344 are planned
  • BAY1895344
  • Pembrolizumab
Dose expansion cohort 1 of BAY1895344ExperimentalParticipants with DDR deficiency biomarker-positive advanced castration-resistant prostate cancer (CRPC), HER2 negative breast cancer (BC), gastric cancer and gynecological cancers including ovarian cancer, fallopian tube and primary peritoneal cancer, who have not received prior treatment with immunotherapy.
  • BAY1895344
  • Pembrolizumab
Dose expansion cohort 2 of BAY1895344ExperimentalParticipants with DDR deficiency biomarker-positive advanced solid tumors where pembrolizumab and/or other anti-PD-1/PDL1 monoclonal antibody treatment is indicated (non-small cell lung cancer (NSCLC), urothelial cancer, renal cancer, hepatocellular cancer and gastric cancer). Participants must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
  • BAY1895344
  • Pembrolizumab

Eligibility Criteria

        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.

          -  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 the following 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 the following laboratory
             tests to be conducted within 7 days before the first dose of study intervention.

          -  Participants must have adequate coagulation, as assessed by the below mentioned
             laboratory tests as applicable, (to be conducted within 7 days before the first dose
             of study intervention) or 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Cmax of BAY1895344
Time Frame:Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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.
Measure:Incidence of Complete response (CR)
Time Frame:Up to 24 months
Safety Issue:
Description:Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
Measure:Incidence of partial response (PR)
Time Frame:Up to 24 months
Safety Issue:
Description:Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
Measure:Incidence of stable disease (SD)
Time Frame:Up to 24 months
Safety Issue:
Description:Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
Measure:Incidence of progressive disease (PD)
Time Frame:Up to 24 months
Safety Issue:
Description:Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)
Measure:Objective Response Rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Trial Keywords

  • DDR (Deoxyribonucleic acid damage repair),
  • ATR (ataxia-telangiectasia and Rad3 related protein)inhibitor,

Last Updated