Advanced Solid TumorPhase 1NCT03188965
First-in-human Study of ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas
A Phase 1 study testing Elimusertib (BAY1895344) in people with Advanced Solid Tumor and Non-Hodgkin's Lymphoma, run by Bayer at 29 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- Elimusertib (BAY1895344)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 229 participants
- Where
- 29 sitesin 7 countries
- Study dates
- 6 Jul 2017to 13 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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
Who cannot join
- 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
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- 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).
Trial locations and contacts
29 sites in 7 countries.
29 sites in 7 countries
United States14 sites
Emory University
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114-2696
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Gabrail Cancer Center
Canton, Ohio, 44718
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
City of Hope National Medical Center
Duarte, California, 91010
US Oncology / Eugene
Eugene, Oregon, 97401
Fairfax-Northern Virginia Hematology/Oncology, PC
Fairfax, Virginia, 22031
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4009
Weill Cornell Medical College
New York, New York, 10021
Jefferson Medical College
Philadelphia, Pennsylvania, 19107
University of Utah - Oncology
Salt Lake City, Utah, 84112
Texas Oncology- San Antonio Northeast
San Antonio, Texas, 78217
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
Canada3 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
OHRI - The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Integrated Cancer Center of the CHU de Québec
Québec, G1J 1Z4
Japan3 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Shizuoka Cancer Center
Sunto, Shizuoka, 411-8777
Switzerland3 sites
Oncology Institute of Southern Switzerland
Bellinzona, 6500
Hôpital Cantonal Universitaire de Genève
Geneva, Canton of Geneva, 1205
Kantonsspital St. Gallen
Sankt Gallen, Canton of St. Gallen, 1009
United Kingdom3 sites
Velindre Hospital
Cardiff, South Glamorgan, CF14 2TL
Freeman Hospital
Newcastle upon Tyne, Tyne and Wear, NE7 7DN
Royal Marsden NHS Trust (Surrey)
Sutton, Surrey, SM2 5PT
Singapore2 sites
National University Hospital
Singapore, 119228
National Cancer Center Singapore
Singapore, 168583
About this study
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
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.
- Being tested
- Elimusertib (BAY1895344)
- Keywords
- First in human, Solid tumors, Lymphomas, Dose escalation, Dose expansion
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Mantle-Cell, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Elimusertib (BAY1895344)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A: single-agent dose-escalation | Experimental | Patients with histologically confirmed solid tumors or non-Hodgkin's lymphoma (NHL) receive BAY1895344 in a 21-day cycle. Receives: Drug: Elimusertib (BAY1895344) |
| Part A.1: Single-agent dose escalation with alternative dosing schedule | Experimental | 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. Receives: Drug: Elimusertib (BAY1895344) |
| J-arm of Part A: dose escalation cohort in Japanese patients | Experimental | Japanese patients with histologically confirmed solid tumors receive BAY1895344 at two dose levels: MTD-1 and MTD. Receives: Drug: Elimusertib (BAY1895344) |
| Part B: single-agent expansion | Experimental | 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. Receives: Drug: Elimusertib (BAY1895344) |
| Part B.1: single-agent expansion with alternative dosing schedule | Experimental | Patients with histologically confirmed relapsed or refractory MCL receive BAY1895344 at a dose determined after evaluation of multiple BAY1895344 doses in Part A.1 Receives: Drug: Elimusertib (BAY1895344) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D) of BAY1895344
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.
Measured: Up to 6 months, minimum: 1 cycle (= 21days)
Incidence of DLTs during Cycle 1 in dose-escalation cohorts during Part A of the study
Measured: During Cycle 1, 1 cycle=21 days
Incidence of DLTs during Cycle 1 in dose-escalation cohorts during Part A.1 of the study
Measured: During Cycle 1, 1 cycle=28 days
Incidence of DLTs during Cycle 1 in dose-escalation cohorts during J-arm of the study
Measured: During Cycle 1, 1 cycle=21 days
The incidence of serious and nonserious treatment-emergent adverse events (TEAEs)
Measured: 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
AUC(0-12) and AUC(0-12)md will be evaluated in Part A, A.1 and J-arm of Part A.
Measured: 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
Maximum observed drug concentration in plasma of BAY1895344 after single-dose (Cmax) and multiple-dose administrations (Cmax,md) in Cycle 1
Cmax and Cmax,md will be evaluated in Part A, A.1 and J-arm of Part A.
Measured: 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
Secondary outcomes (3)
Incidence of solid tumor responses (except CRPC) consistent with the RECIST 1.1 criteria
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
Measured: Through study completion, an average of 4 months
Incidence of lymphoma responses consistent with the Lugano Classification
Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease).
Measured: Through study completion, an average of 4 months
Incidence of CRPC tumor responses consistent with the recommendations of the PCWG3
Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease).
PCWG3: Prostate Cancer Working Group 3
Measured: Through study completion, an average of 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2017
- Study start6 Jul 2017
- Primary completion2 Dec 2022
- Study completion13 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 229 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03188965
- Sponsor's protocol ID
- 18594
- Other IDs
- 2016-004484-39, 2016
- Status last verified
- Oct 2023
- First submitted
- 14 Jun 2017
- Last updated
- 11 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
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.
PubMed 32502336
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03188965
- Acronym / sponsor ID
- 18594
- Keywords
- First in human, Solid tumors, Lymphomas, Dose escalation, Dose expansion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 229 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 6 Jul 2017 (actual)
- Primary completion
- 2 Dec 2022 (actual)
- Study completion
- 13 Sep 2023 (actual)
- First posted
- 16 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: single-agent dose-escalation | Experimental | Drug: Elimusertib (BAY1895344)Patients with histologically confirmed solid tumors or non-Hodgkin's lymphoma (NHL) receive BAY1895344 in a 21-day cycle. |
| Part A.1: Single-agent dose escalation with alternative dosing schedule | Experimental | Drug: Elimusertib (BAY1895344)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. |
| J-arm of Part A: dose escalation cohort in Japanese patients | Experimental | Drug: Elimusertib (BAY1895344)Japanese patients with histologically confirmed solid tumors receive BAY1895344 at two dose levels: MTD-1 and MTD. |
| Part B: single-agent expansion | Experimental | Drug: Elimusertib (BAY1895344)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. |
| Part B.1: single-agent expansion with alternative dosing schedule | Experimental | Drug: Elimusertib (BAY1895344)Patients with histologically confirmed relapsed or refractory MCL receive BAY1895344 at a dose determined after evaluation of multiple BAY1895344 doses in Part A.1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
- 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.
- 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.
- 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.
Key exclusion criteria (14 listed)
- 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：
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | J-arm of Part A: dose escalation cohort in Japanese patients, Part A.1: Single-agent dose escalation with alternative dosing schedule, Part A: single-agent dose-escalation, Part B.1: single-agent expansion with alternative dosing schedule, Part B: single-agent expansion |
Primary outcome
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.
3 secondary outcomes
Incidence of solid tumor responses (except CRPC) consistent with the RECIST 1.1 criteria
Time frame: Through study completion, an average of 4 months
Incidence of lymphoma responses consistent with the Lugano Classification
Time frame: Through study completion, an average of 4 months
Incidence of CRPC tumor responses consistent with the recommendations of the PCWG3
Time frame: Through study completion, an average of 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
- Derived from this study: PubMed 32502336Lucking 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.
- Individual participant dataSharing planned: No. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
29 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Elimusertib (BAY1895344) in people with Advanced Solid Tumor and Non-Hodgkin's Lymphoma, run by Bayer at 29 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Canada, Japan, Switzerland, United Kingdom and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03188965, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2023.