Description:
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.
Title
- Brief Title: First-in-human Study of ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas
- 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
Clinical Trial IDs
- ORG STUDY ID:
18594
- SECONDARY ID:
2016-004484-39
- NCT ID:
NCT03188965
Conditions
Interventions
Drug | Synonyms | Arms |
---|
BAY1895344 | | Dose escalation of BAY1895344 in Part A |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose escalation of BAY1895344 in Part A | Experimental | Single-agent dose-escalation part. Part A has the objective to define the MTD and / or RP2D. | |
J-arm of Part A | Experimental | 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. | |
Dose expansion of BAY1895344 in Part B | Experimental | 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. | |
Part A.1: Single-agent dose escalation part | Experimental | 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. | |
Eligibility 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 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.
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. 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):
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
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) |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease) RECIST (Response Evaluation Criteria in Solid Tumors) |
Measure: | 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 |
Safety Issue: | |
Description: | CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease) |
Measure: | 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 |
Safety Issue: | |
Description: | CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease) |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Bayer |
Trial Keywords
- First in human
- Solid tumors
- Lymphomas
- Dose escalation
- Dose expansion
Last Updated
August 18, 2021