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First-in-human Study of ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas

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ClinicalTrials.gov Identifier: NCT03188965
Recruitment Status : Recruiting
First Posted : June 16, 2017
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
The ATR(ataxia-telangiectasia and Rad3 related protein) inhibitor BAY1895344 is developed for the treatment of patients with advanced solid tumors and lymphomas. The purpose of the proposed trial is to evaluate the safety and tolerability of BAY1895344, and to identify the maximum tolerated dose of BAY1895344 that could be safely given to cancer patients. Further, the response of the cancer to the treatment will be determined.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: BAY1895344 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, First-in-human, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Maximum Tolerated Dose and / or Recommended Phase II Dose of the ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas
Actual Study Start Date : July 6, 2017
Estimated Primary Completion Date : September 3, 2020
Estimated Study Completion Date : October 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Dose escalation of BAY1895344 in Part A
Single-agent dose-escalation part. Part A has the objective to define the MTD and / or RP2D.
Drug: BAY1895344
Study drug will be administered as scheduled.

Experimental: J-arm of Part A
Single-agent dose-escalation part in Japanese patients. J-arm has the objective to confirm the MTD (or RP2D) dose is safe and tolerable in Japanese patients.
Drug: BAY1895344
Study drug will be administered as scheduled.

Experimental: Dose expansion of BAY1895344 in Part B
Single-agent expansion part. Once the MTD has been defined, safety, PK profile, PD of target engagement, and preliminary efficacy will be further evaluated in Part B of the study. Once the MTD dose has been confirmed is safe and tolerable in Japanese patients, safety, PK profile, PD of target engagement, and preliminary efficacy will be further evaluated in Part B of the study.
Drug: BAY1895344
Study drug will be administered as scheduled.

Experimental: Part A.1: Single-agent dose escalation part
Part A.1 - single-agent dose escalation part with alternative dosing schedule Patients with histologically confirmed solid tumors or NHL known to be positive for ATM loss and/or ATM deleterious mutations will be included.
Drug: BAY1895344
Study drug will be administered as scheduled.




Primary Outcome Measures :
  1. The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D) of BAY1895344 [ Time Frame: Up to 6 months, minimum: 1 cycle (= 21days) ]
    Dose-escalation cohort during Part A. The MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during cycle 1 is below 30%, or the maximum dose tested, whichever is achieved first in the dose-escalation cohorts during Part A of the study.

  2. Incidence of DLTs during Cycle 1 in dose-escalation cohorts during Part A of the study [ Time Frame: During cycle 1, 1 cycle=21 days ]
  3. Incidence of DLTs during Cycle 1 in dose-escalation cohorts during Part A.1 of the study [ Time Frame: During cycle 1, 1 cycle=28 days ]
  4. Incidence of DLTs during Cycle 1 in dose-escalation cohorts during J-arm of the study [ Time Frame: During cycle 1, 1 cycle=21 days ]
  5. The incidence of serious and nonserious treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 30 days after end of treatment ]
  6. AUC (area under the plasma concentration of BAY1895344 vs. time curve) from zero to 12 hours after single-dose (C1D1) and multiple-dose administrations (C1D10) [ Time Frame: At day 1 and day 10 of first cycle ]
    In Part A, A.1, J-arm of Part A and Part B. Analysis of drug exposure and pharmacokinetic parameters in patients over a course of time

  7. Cmax of BAY1895344 in cycle 1 after single-dose (C1D1) and multiple-dose administrations (C1D10) [ Time Frame: At day 1 and day 10 of first cycle ]
    In Part A, A.1, J-arm of Part A and Part B. To support profiling pharmacokinetic of study drug in patients


Secondary Outcome Measures :
  1. Incidence of patients with CR, PR, SD or PD (except for patients with castration resistant prostate cancer) consistent with the RECIST 1.1 criteria [ Time Frame: Through study completion, an average of 4 months ]
    CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease) RECIST (Response Evaluation Criteria in Solid Tumors)

  2. Incidence of lymphoma patients with CR, PR, SD or PD consistent with the Lugano Classification [ Time Frame: Through study completion, an average of 4 months ]
    CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)

  3. Incidence of castration resistant prostate cancer patients with CR, PR, SD or PD consistent with the recommendations of the Prostate Cancer Working Group 3 (PCWG3) [ Time Frame: Through study completion, an average of 4 months ]
    CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)



Information from the National Library of Medicine

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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:

Part A - single-agent dose-escalation part:

- Patients with histologically confirmed solid tumors or non-Hodgkin's lymphoma (NHL).

J-arm of Part A - single-agent dose escalation in Japanese

- Japanese patients with histologically confirmed solid tumors. Patients with tumors known to be positive for DDR (deoxyribonucleic acid damage repair) defects (such as ATM (ataxia-telangiectasia mutated) deleterious mutation or low ATM expression) can be included.

Part B - single-agent expansion part:

  • Patients with DDR deficiency biomarker-positive advanced solid tumors of the following histologies: i) CRPC (castration-resistant prostate cancer); ii) HER2-negative BC that is hormone-receptor positive (estrogen-receptor positive, progesterone-receptor positive, or both) or TNBC (triple negative BC); iii) CRC (colorectal cancer), and iv) gynecological tumors (ovarian, primary peritoneal, and fallopian tube cancers, endometrial cancer, or cervical cancer).
  • The biomarker status of patients in Part B will be evaluated before general screening and only patients with the presence of the putative biomarkers of DDR deficiency will be recruited into general screening.
  • Patients with histologically confirmed advanced cancer, regardless of the cancer type, or NHL and loss of ATM protein by IHC.

The following inclusion criteria apply to ALL (dose-escalation and expansion) patients:

  • Patients with tumors resistant or refractory to standard treatment and in which, in the opinion of the investigator, experimental treatment with BAY1895344 may be of benefit, Furthermore, no standard therapy would confer clinical benefit to the patient.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Patients must have adequate bone marrow function as assessed by the following laboratory tests to be conducted within 7 (+2) days before the first dose of study drug:

The below values are to be independent of red blood cell transfusions or granulocytes colony-stimulating factor (G-CSF) (i.e., no red blood cell or platelets transfusion within 28 days prior to the screening complete blood count (CBC) result, or administration of G-CSF is to occur within 14 days prior to the CBC result):

  1. Hemoglobin ≥ 9 g/dL; patients with chronic erythropoietin treatment consistent with institutional guidelines can be included.
  2. Absolute neutrophil count (ANC) ≥ 1.5X10* 9/L (≥ 1500/mm*3)
  3. Platelet count ≥ 100X10*9/L (≥100,000/mm*3)

Exclusion Criteria:

  • Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study
  • 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)
  • Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C
  • Patients with known human immunodeficiency virus (HIV) infection
  • Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator's discretion provided that the disease is stable and sufficiently controlled under treatment.
  • Infections of CTCAE(Common Terminology Criteria for Adverse Events Version) Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade >2

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): NCT03188965


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

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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: NCT03188965     History of Changes
Other Study ID Numbers: 18594
2016-004484-39 ( EudraCT Number )
First Posted: June 16, 2017    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
First in human
Solid tumors
Lymphomas
Dose escalation
Dose expansion
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases