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.
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
Drug | Synonyms | Arms |
---|
BAY1895344 | | Dose escalation of BAY1895344 and fixed dose of Niraparib |
Niraparib | | Dose 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
Name | Type | Description | Interventions |
---|
Dose escalation of BAY1895344 and fixed dose of Niraparib | Experimental | In participants with all solid tumor(excluding prostate cancer) and positive for DDR deficiency.
DDR: DNA-Damage Repair | |
Participants PARPi naïve | Experimental | Participants with ovarian cancer, PARPi naïve and with a platinum resistant/refractory disease and DDR deficiency.
DDR: DNA-Damage Repair | |
Participants with disease progression on PARPi | Experimental | Participants with ovarian cancer and disease progression on PARPi | |
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: | Recruiting |
Lead Sponsor: | Bayer |
Last Updated
August 26, 2021