Breast Cancer Clinical Trial

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

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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Part A - single-agent dose-escalation:

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

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 defects (such as ATM deleterious mutation or low ATM expression) can be included.

Part A.1 - single-agent dose-escalation 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. The biomarker status of patients in Part A.1 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.

Part B - single-agent expansion:

Patients with DDR deficiency biomarker-positive advanced solid tumors of the following histologies: i) CRPC; ii) HER2-negative BC that is hormone-receptor positive (estrogen-receptor positive, progesterone-receptor positive, or both) or TNBC; iii) CRC, and iv) gynecological tumors (ovarian, primary peritoneal, and fallopian tube cancers, endometrial cancer, or cervical cancer).
Patients with histologically confirmed advanced solid cancer, regardless of the cancer type, or NHL and loss of ATM protein by IHC.
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.

Part A.1 And Part B:

- Patients must be able to provide either samples of archival tumor tissue not older than 6 months or a fresh tumor biopsy during general screening.

Part B.1 - single-agent expansion with alternative dosing schedule:

- Patients with histologically confirmed R/R MCL. These patients do not undergo biomarker testing to determine eligibility. The provision of baseline tumor tissue (archival or fresh) is strongly encouraged. If archival tissue ≤ 6 months old is unavailable, a fresh baseline biopsy may be obtained if safe and feasible.

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. Patients in the MCL cohort of Part B.1 are to be relapsed or refractory to standard treatments.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For MCL patients: ECOG of 0 to 2.

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. Note that 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). Requirements for MCL patients are indicated below.

a. Hemoglobin ≥ 9 g/dL. Patients with chronic erythropoietin treatment consistent with institutional guidelines can be included. For MCL patients: ≥ 8 g/dL; red blood cell transfusions during the screening period are allowed, and patients with chronic erythropoietin treatment consistent with institutional guidelines can be included
b. Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L (≥ 1500/mm^3). For MCL patients: ANC ≥ 1.0 X 10^9/L. Patients with ANC ≤ 1.0 X 10^9/L due to marrow infiltration may receive G-CSF during screening to bring pretreatment ANC levels to ≥ 1.0 X 10^9/L
c. Platelet count ≥ 100 X 10^9/L (≥100,000/mm^3). For MCL patients: ≥ 75 X 10^9/L

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

Known human immunodeficiency virus (HIV)-infected persons are not eligible if any of the following criteria apply:

CD4+ T-cell count less than 350 cells/μL
History of AIDS-defining opportunistic infection within the past 12 months
On established antiretroviral therapy (ART) for less than 4 weeks or presenting with a viral load of more than 400 copies/mL prior to enrollment
On ART or prophylactic antimicrobials that are expected to cause significant drug-drug interactions or overlapping toxicities with study intervention
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 Common Terminology Criteria for Adverse Events Version (CTCAE) Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade > 2
Metastatic solid brain, spinal, or meningeal tumors or central nervous system (CNS) lymphoma manifestations (including meningeosis lymphomatosa and parenchymal lymphoma lesions) unless the patient is > 3 months from definitive therapy, has a stable imaging study within 4 weeks prior to the first dose of study drug and is clinically stable with respect to the tumor at the time of study entry. Patients with asymptomatic brain metastases must not be on steroid therapy. Patients with neurological symptoms should undergo a CT / MRI scan of the brain or spinal column to exclude new or progressive brain, meningeal, or spinal metastases or CNS lymphoma manifestations.
History of organ allograft transplantation. For MCL patients: Those who received an allogeneic stem cell transplant may participate provided that engraftment has occurred, there is no evidence of GVHD, and the patient is not taking immune suppressants. MCL patients who received an autologous stem cell transplant may participate once they have recovered from the procedure.
Treatment with anticancer chemotherapy or immunotherapy during the study or within 3 weeks before the first dose of study drug. For small-molecule drugs, a period of at least 3 half-lives before the first dose of study drug is acceptable. Mitomycin C or nitrosoureas should not be given within 6 weeks before the first dose of study drug.
Treatment with systemic steroids (methylprednisolone dose ≥10 mg/day or equivalent dose). For MCL patients: Treatment with systemic corticosteroids > 20 mg/day prednisone equivalent (unless patient has been taking a stable dose for >3 weeks and has shown tumor progression).

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

239

Study ID:

NCT03188965

Recruitment Status:

Recruiting

Sponsor:

Bayer

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There are 46 Locations for this study

See Locations Near You

City of Hope National Medical Center
Duarte California, 91010, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa Florida, 33612, United States
Emory University
Atlanta Georgia, 30322, United States
Massachusetts General Hospital
Boston Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
Weill Cornell Medical College
New York New York, 10021, United States
Gabrail Cancer Center
Canton Ohio, 44718, United States
University Hospitals Cleveland Medical Center
Cleveland Ohio, 44106, United States
University Hospitals Cleveland Medical Center
Cleveland Ohio, 44106, United States
US Oncology / Eugene
Eugene Oregon, 97401, United States
Jefferson Medical College
Philadelphia Pennsylvania, 19107, United States
US Oncology / Fort Worth
Fort Worth Texas, 76014, United States
University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States
Texas Oncology- San Antonio Northeast
San Antonio Texas, 78217, United States
University of Utah - Oncology
Salt Lake City Utah, 84112, United States
Fairfax-Northern Virginia Hematology/Oncology, PC
Fairfax Virginia, 22031, United States
Cross Cancer Institute
Edmonton Alberta, T6G 1, Canada
OHRI - The Ottawa Hospital
Ottawa Ontario, K1H 8, Canada
Integrated Cancer Center of the CHU de Québec
Quebec , G1J 1, Canada
Beijing Cancer Hospital
Beijing , 10014, China
Institut Bergonié - Unicancer Nouvelle Aquitaine
Bordeaux Cedex , 33076, France
Hôpital Henri Mondor
Creteil Cedex , 94000, France
Hôpital Claude Huriez - Lille
Lille Cedex , 59037, France
Hopital Hotel Dieu - Nantes
Nantes Cedex , 44035, France
Centre Antoine Lacassagne
Nice Cedex 2 , 06102, France
Centre Hospitalier Lyon Sud
Pierre Benite , 69495, France
Institut de Cancérologie de l'Ouest - Saint Herblain
Saint Herblain , 44805, France
Institut Claudius Regaud - iUCT Oncopole
Toulouse Cedex 9 , 31059, France
Institut Gustave Roussy
Villejuif , 94805, France
Eberhard-Karls-Universität Tübingen
Tübingen Baden-Württemberg, 72076, Germany
Klinikum der Universität München Grosshadern
München Bayern, 81377, Germany
Universitätsmedizin der Johannes Gutenberg Universität Mainz
Mainz Rheinland-Pfalz, 55131, Germany
Universitätsklinikum Carl Gustav Carus Dresden
Dresden Sachsen, 01307, Germany
National Cancer Center Hospital East
Kashiwa Chiba, 277-8, Japan
Shizuoka Cancer Center
Sunto Shizuoka, 411-8, Japan
National Cancer Center Hospital
Chuo-ku Tokyo, 104-0, Japan
National University Hospital
Singapore , 11922, Singapore
National Cancer Center Singapore
Singapore , 16961, Singapore
Universitätsspital Basel
Basel Basel-Stadt, 4056, Switzerland
Kantonsspital St. Gallen
St. Gallen Sankt Gallen, 9007, Switzerland
Oncology Institute of Southern Switzerland
Bellinzona , 6500, Switzerland
Hôpital Cantonal Universitaire de Genève
Genève , 1205, Switzerland
UniversitätsSpital Zürich
Zürich , 8091, Switzerland
Belfast City Hospital
Belfast North Ireland, BT12 , United Kingdom
Velindre Hospital
Cardiff South Glamorgan, CF14 , United Kingdom
Royal Marsden NHS Trust (Surrey)
Sutton Surrey, SM2 5, United Kingdom
Freeman Hospital
Newcastle Upon Tyne Tyne And Wear, NE7 7, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

239

Study ID:

NCT03188965

Recruitment Status:

Recruiting

Sponsor:


Bayer

How clear is this clinincal trial information?

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