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

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ClinicalTrials.gov Identifier: NCT04267939
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors (Excluding Prostate Cancer) Ovarian Cancer Drug: BAY1895344 Drug: Niraparib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : February 26, 2020
Estimated Primary Completion Date : August 16, 2022
Estimated Study Completion Date : January 8, 2025


Arm Intervention/treatment
Experimental: Dose escalation of BAY1895344 and fixed dose of Niraparib

In participants with all solid tumor(excluding prostate cancer) and positive for DDR deficiency.

DDR: DNA-Damage Repair

Drug: BAY1895344
BAY1895344 will be administered BID (twice daily) in a 28 day-cycle.

Drug: Niraparib
Niraparib will be administered orally once daily continuously throughout the cycle.

Experimental: Participants PARPi naïve

Participants with ovarian cancer, PARPi naïve and with a platinum resistant/refractory disease and DDR deficiency.

DDR: DNA-Damage Repair

Drug: BAY1895344
BAY1895344 will be administered BID (twice daily) in a 28 day-cycle.

Drug: Niraparib
Niraparib will be administered orally once daily continuously throughout the cycle.

Experimental: Participants with disease progression on PARPi
Participants with ovarian cancer and disease progression on PARPi
Drug: BAY1895344
BAY1895344 will be administered BID (twice daily) in a 28 day-cycle.

Drug: Niraparib
Niraparib will be administered orally once daily continuously throughout the cycle.




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Incidence of treatment emergent adverse events (TEAEs) [ Time Frame: Up to 28 days after the last administration of study intervention ]
  3. Severity of treatment emergent adverse events (TEAEs) [ Time Frame: Up to 28 days after the last administration of study intervention ]
  4. Incidence of treatment emergent serious adverse events (TESAEs) [ Time Frame: Up to 28 days after the last administration of study intervention ]
  5. Severity of treatment emergent serious adverse events (TESAEs) [ Time Frame: Up to 28 days after the last administration of study intervention ]
  6. Frequency of Dose Limiting Toxicities at each dose level during the DLT observation period for Cycle 1 [ Time Frame: 28 days after first administration of study intervention (Cycle 1) ]
    Maximum tolerated dose (MTD)


Secondary Outcome Measures :
  1. Incidence of participants with complete response (CR) [ Time Frame: Up to 24 months ]
  2. Incidence of participants with partial response (PR) [ Time Frame: Up to 24 months ]
  3. Incidence of participants with stable disease (SD) [ Time Frame: Up to 24 months ]
  4. Incidence of participants with progressive disease (PD) [ Time Frame: Up to 24 months ]
  5. Objective response rate (ORR) [ Time Frame: Up to 24 months ]
  6. Disease control rate (DCR) [ Time Frame: Up to 24 months ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
    AUC: Area under the curve



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04267939


Contacts
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Contact: Bayer Clinical Trials Contact (+) 1-888-8422937 clinical-trials-contact@bayer.com

Locations
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United States, Massachusetts
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan-Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT04267939    
Other Study ID Numbers: 18595
2018-003930-34 ( EudraCT Number )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: April 1, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
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.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents