June 14, 2017
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June 16, 2017
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October 11, 2023
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July 6, 2017
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December 2, 2022 (Final data collection date for primary outcome measure)
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- The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D) of BAY1895344 [ Time Frame: Up to 6 months, minimum: 1 cycle (= 21days) ]
MTD and/or R2PD will be determined in Cycle 1 of Part A, Part A.1 and J-arm of 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 during dose-escalation.
- 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 ]
- 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 ]
- 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 ]
- The incidence of serious and nonserious treatment-emergent adverse events (TEAEs) [ Time Frame: After first administration of study drug up to 30 days after the last dose of study drug ]
- Area under the plasma concentration of BAY1895344 vs. time curve from zero to 12 hours after single-dose (AUC[0-12]) and multiple-dose administrations (AUC[0-12]md) in Cycle 1 [ Time Frame: Pre-dose and up to 12 hours post-dose at Day 1 of Cycle 1 and Day 10 (Part A and J-arm) or Day 17 (Part A.1) of Cycle 1 ]
AUC(0-12) and AUC(0-12)md will be evaluated in Part A, A.1 and J-arm of Part A.
- Maximum observed drug concentration in plasma of BAY1895344 after single-dose (Cmax) and multiple-dose administrations (Cmax,md) in Cycle 1 [ Time Frame: Pre-dose and up to 12 hours post-dose at Day 1 of Cycle 1 and Day 10 (Part A and J-arm) or Day 17 (Part A.1) of Cycle 1 ]
Cmax and Cmax,md will be evaluated in Part A, A.1 and J-arm of Part A.
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- The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D) of BAY1895344 [ Time Frame: Up to 6 months, minimum: 1 cycle (=21days) ]
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.
- The incidence of serious and nonserious treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 23 months, minimum: 1 cycle (=21days) ]
Assessment of safety parameters (such as ECG, vital signs… etc.) which is deemed relating to study drug.
- AUC (area under the plasma concentration of BAY1895344 vs. time curve) from zero to 12 hours after single (first) dose of BAY1895344 [ Time Frame: At day 1 and day 10 of first cycle ]
Analysis of drug exposure and pharmacokinetic parameters in patients over a course of time
- 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 ]
To support profiling pharmacokinetic of study drug in patients
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- Incidence of solid tumor responses (except CRPC) consistent with the RECIST 1.1 criteria [ Time Frame: Through study completion, an average of 4 months ]
Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease). CRPC: castration resistant prostate cancer; RECIST: Response Evaluation Criteria in Solid Tumors
- Incidence of lymphoma responses consistent with the Lugano Classification [ Time Frame: Through study completion, an average of 4 months ]
Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease).
- Incidence of CRPC tumor responses consistent with the recommendations of the PCWG3 [ Time Frame: Through study completion, an average of 4 months ]
Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease).
PCWG3: Prostate Cancer Working Group 3
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- 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: Up to 23 months or until discontinuation of study, whichever comes first ]
CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease) RECIST (Response Evaluation Criteria in Solid Tumors)
- Incidence of lymphoma patients with CR, PR, SD or PD consistent with the Lugano Classification [ Time Frame: Up to 23 months or until discontinuation of study, whichever comes first ]
CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)
- 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: Up to 23 months or until discontinuation of study, whichever comes first ]
CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)
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Not Provided
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Not Provided
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First-in-human Study of ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas
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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
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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.
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Not Provided
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Interventional
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Phase 1
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Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Advanced Solid Tumor
- Non-Hodgkin's Lymphoma
- Mantle Cell Lymphoma
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Drug: Elimusertib (BAY1895344)
Solution or tablet, oral, to be administered until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator.
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- Experimental: Part A: single-agent dose-escalation
Patients with histologically confirmed solid tumors or non-Hodgkin's lymphoma (NHL) receive BAY1895344 in a 21-day cycle.
Intervention: Drug: Elimusertib (BAY1895344)
- Experimental: 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 receive BAY1895344 in a 28-day cycle.
Intervention: Drug: Elimusertib (BAY1895344)
- Experimental: J-arm of Part A: dose escalation cohort in Japanese patients
Japanese patients with histologically confirmed solid tumors receive BAY1895344 at two dose levels: MTD-1 and MTD.
Intervention: Drug: Elimusertib (BAY1895344)
- Experimental: Part B: single-agent expansion
Patients with a) DDR deficiency biomarker-positive advanced solid tumors: castration-resistant prostate cancer (CRPC), HER2-negative breast cancer (BC), colorectal cancer (CRC), and gynecological tumors; OR b) histologically confirmed advanced cancer and loss of ATM regardless of the cancer type receive BAY1895344 at MTD determined at the end of dose escalation.
Intervention: Drug: Elimusertib (BAY1895344)
- Experimental: Part B.1: single-agent expansion with alternative dosing schedule
Patients with histologically confirmed relapsed or refractory MCL receive BAY1895344 at a dose determined after evaluation of multiple BAY1895344 doses in Part A.1
Intervention: Drug: Elimusertib (BAY1895344)
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Lucking U, Wortmann L, Wengner AM, Lefranc J, Lienau P, Briem H, Siemeister G, Bomer U, Denner K, Schafer M, Koppitz M, Eis K, Bartels F, Bader B, Bone W, Moosmayer D, Holton SJ, Eberspacher U, Grudzinska-Goebel J, Schatz C, Deeg G, Mumberg D, von Nussbaum F. Damage Incorporated: Discovery of the Potent, Highly Selective, Orally Available ATR Inhibitor BAY 1895344 with Favorable Pharmacokinetic Properties and Promising Efficacy in Monotherapy and in Combination Treatments in Preclinical Tumor Models. J Med Chem. 2020 Jul 9;63(13):7293-7325. doi: 10.1021/acs.jmedchem.0c00369. Epub 2020 Jun 28.
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Completed
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229
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210
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September 13, 2023
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December 2, 2022 (Final data collection date for primary outcome measure)
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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.
- Patients must have measurable disease (as per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] or the Lugano classification as applicable, with the exception of prostate cancer patients who must have measurable or evaluable disease per the recommendations of the Prostate Cancer Clinical Trial Working Group 3 [PCWG3]).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For MCL patients: ECOG of 0 to 2.
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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:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Canada, China, Japan, Singapore, Switzerland, United Kingdom, United States
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France, Germany
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NCT03188965
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18594 2016-004484-39 ( EudraCT Number )
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No
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
No |
Plan Description: |
Availability of this study's data will later 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.vivli.org 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 member section of the portal. |
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Bayer
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Same as current
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Bayer
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Same as current
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Not Provided
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Study Director: |
Bayer Study Director |
Bayer |
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Bayer
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October 2023
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