Clinical Trials /

ATR Inhibitor BAY 1895344 Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer

NCT04267939

Description:

The purpose of the study is to test how well patients with advanced solid tumors and ovarian cancer respond to treatment with BAY1895344 in combination with niraparib. In addition researchers want to find for patients the optimal dose of BAY1895344 in combination with niraparib, 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 produced by the body (ATR Kinase) which is important for the growth of tumor cells. Niraparib works by blocking a substance produced by the body (PARP enzymes) in a way that tumor cells can be killed, or made more susceptible to chemotherapy.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: ATR Inhibitor BAY 1895344 Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer
  • Official Title: An Open-label Phase 1b Study to Determine the Maximum Tolerated and/or Recommended Phase 2 Dose of the ATR Inhibitor BAY 1895344 in Combination With PARP Inhibitor Niraparib, in Patients With Recurrent Advanced Solid Tumors and Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18595
  • SECONDARY ID: 2018-003930-34
  • NCT ID: NCT04267939

Conditions

  • Advanced Solid Tumors (Excluding Prostate Cancer)
  • Ovarian Cancer

Interventions

DrugSynonymsArms
BAY1895344Dose escalation of BAY1895344 and fixed dose of Niraparib
NiraparibDose escalation of BAY1895344 and fixed dose of Niraparib

Purpose

The purpose of the study is to test how well patients with advanced solid tumors and ovarian cancer respond to treatment with BAY1895344 in combination with niraparib. In addition researchers want to find for patients the optimal dose of BAY1895344 in combination with niraparib, 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 produced by the body (ATR Kinase) which is important for the growth of tumor cells. Niraparib works by blocking a substance produced by the body (PARP enzymes) in a way that tumor cells can be killed, or made more susceptible to chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of BAY1895344 and fixed dose of NiraparibExperimentalIn participants with all solid tumor(excluding prostate cancer) and positive for DDR deficiency. DDR: DNA-Damage Repair
  • BAY1895344
  • Niraparib
Participants PARPi naïveExperimentalParticipants with ovarian cancer, PARPi naïve and with a platinum resistant/refractory disease and DDR deficiency. DDR: DNA-Damage Repair
  • BAY1895344
  • Niraparib
Participants with disease progression on PARPiExperimentalParticipants with ovarian cancer and disease progression on PARPi
  • BAY1895344
  • Niraparib

Eligibility Criteria

        Inclusion Criteria:

          -  Participant must be ≥ 18 years of age, at the time of signing the informed consent.

          -  Participants must have histologically confirmed diagnosis of the following indications
             as described below:

             -- Dose escalation (Part A): recurrent advanced solid tumors, excluding prostate
             cancer, who experienced disease progression after treatment with all available
             standard of care therapies for metastatic disease Participants must have DDR
             deficiency in their tumors. -- Dose expansion (Part B): recurrent EOC, fallopian tube
             or primary peritoneal cancer

               -  Sub-population 1: participants PARPi naïve and with a
                  platinum-resistant/refractory disease (recurrence with a PFI < 6 months from last
                  platinum-based regimen). Participants may not have had more than 3 prior
                  therapies since the development of platinum resistance.

               -  Sub-population 2: participants with disease progression on PARPi (including
                  niraparib), administered as maintenance as well active line of therapy.
                  Participants must have not received further line of therapy after disease
                  progression on PARPi.

          -  Participants in Part A and sub-population 1of part B of the study will need to have
             DDR deficiency in their tumors.Sub-population 2 of Part B will be BM unselected (BM
             analysis only retrospective).

          -  Participants must have disease progression and measurable disease, as defined by
             RECIST 1.1.

          -  Archival tissue must not be older than 12 months, otherwise fresh tumor tissue samples
             at baseline are mandatory.

          -  ECOG PS of 0 to 1

          -  Life expectancy of at least 12 weeks

          -  Adequate bone marrow function as assessed by the following laboratory tests to be
             conducted within 7 ( ±2) days before the first dose of study intervention:

               -  Hemoglobin (Hb) ≥ 10 g/dL

               -  Platelet count ≥ 150 x 109/L ( ≥150,000/mm*3)

               -  Absolute neutrophil count (ANC) ≥ 2.0 x 109/L ( ≥ 2000/mm*3)

          -  Participants must have adequate organ function.

          -  Participants must have adequate coagulation.

          -  Adequate cardiac function per institutional normal measured by echocardiography
             (recommended) or MUGA scan/cardiac MRI per institutional guidelines.

          -  A female participant is eligible to participate if she is not pregnant (confirmed by a
             negative serum pregnancy test within 7(±2)days of first study intervention), not
             breastfeeding, or is not a woman of childbearing potential (WOCBP). Participants must
             agree to use highly effective contraception during the intervention period and for at
             least 6 months (180 days) after intervention

        Exclusion Criteria:

          -  Inability to swallow oral medication

          -  Known hypersensitivity to BAY1895344 and/or niraparib or excipients of the
             preparations or any agent given in association with this study

          -  History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis

          -  Ongoing or active uncontrolled infection (bacterial, fungal, or viral; e.g. hepatitis
             viral) of CTCAE grade ≥ 2 that requires systemic treatment

          -  Known history of HIV infection (HIV 1/2 antibodies)

          -  Immunocompromised participants (e.g. diagnosis of immunodeficiency or ongoing
             immunosuppressive therapy)

          -  Pleural effusion or ascites that causes respiratory compromise (CTCAE grade ≥ 2
             dyspnea)

          -  Active HBV or HCV infection that requires treatment.

          -  Moderate or severe hepatic impairment, i.e. Child Pugh Class B or C

          -  Participants with significant cardiovascular disease and/or relevant findings are
             excluded:

          -  History of cardiac disease: congestive heart failure 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).

          -  Clinically relevant findings in the ECG such as a second- or third-degree
             atrioventricular block, prolongation of the QRS complex ≥ 120 ms, or prolongation of
             the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise between the
             investigator and the sponsor's medically responsible person.

          -  Previous treatment with an ATR Inhibitor

          -  Previous treatment with known or putative PARPi, if discontinued for CTCAE grade ≥ 3
             AEs or CTCAE grade ≥ 3 hypersensitivity to PARPi
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D) of BAY1895344
Time Frame:Up to 28 days after last administration of study Intervention
Safety Issue:
Description:The MTD is defined as the highest dose level that can be given so that the toxicity probability is closest to the target toxicity PT=30% or as the maximum tested dose, whichever is achieved first during Cycle 1. Estimation of the MTD will be based on the estimation of the observed dose-dependent incidence rate of DLT in Cycle 1.

Secondary Outcome Measures

Measure:Incidence of participants with complete response (CR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence of participants with partial response (PR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence of participants with stable disease (SD)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence of participants with progressive disease (PD)
Time Frame:Up to 24 months
Safety Issue:
Description:
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:
Measure:Cmax (Maximal plasma exposure) of BAY1895344 after single dose administration
Time Frame:Pre-dose, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours post-dose on Cycle 1, Day 1
Safety Issue:
Description:
Measure:AUC(0-12) of BAY1895344 after single dose administration
Time Frame:Pre-dose, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours post-dose on Cycle 1, Day 1
Safety Issue:
Description:
Measure:Cmax,md of BAY1895344 after multiple dose administration
Time Frame:Pre-dose, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours post-dose on Cycle 1, Day 17
Safety Issue:
Description:
Measure:AUC(0-12)md of BAY1895344 after multiple dose administration
Time Frame:Pre-dose, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours post-dose on Cycle 1, Day 17
Safety Issue:
Description:AUC: Area under the curve

Details

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

Last Updated

February 11, 2020