Phase I Trial of BAY1251152 for Advanced Blood Cancers

Study Overview
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Brief Summary
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The purpose of this study is to identify the most appropriate dose that can be safely administered and that can have an effect on blood cancer cells. Once that safe dose is identified, additional patients will be asked to join the study to further evaluate the safety and effectiveness of the study drug. The study will also investigate the pharmacokinetics (study of what the body does to the drug), as well as pharmacodynamics (study of what the drug does to the body), which may provide information about the effects of BAY 1251152. The study will also measure some biological markers (markers of biological activity in your body) that can be used to predict the response and safety of the proposed treatment.

Official Title
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An Open-label, Multicenter Phase I Study to Characterize the Safety, Tolerability, Preliminary Anti-tumor Activity, Pharmacokinetics and Maximum Tolerated Dose of BAY1251152 in Patients With Advanced Hematological Malignancies

Conditions
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Hematologic Neoplasms

Intervention / Treatment
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* Drug: BAY1251152


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged ≥18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and Life expectancy of at least 12 weeks Patients are able and willing to provide bone marrow biopsies/aspirates as requested by the protocol Patients with confirmed advanced hematological malignancies Negative serum pregnancy test Women and men of reproductive potential must agree to use highly effective contraception when sexually active. Ability to understand and the willingness to sign a written informed consent. Patients must have adequate coagulation (international normalized ratio (INR) or prothrombin time (PT), partial thromboplastin time (PTT) ≤1.5 times ULN) Adequate liver function (total bilirubin ≤ 1.5 times the ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN Exclusion Criteria: Presence of active/uncontrolled central nervous system involvement History of clinically significant cardiac disease; uncontrolled hypertension Left ventricular ejection fraction (LVEF) < 45% Allogeneic stem cell transplant within 100 days before first dose of study drug Known history of human immunodeficiency virus (HIV) infection Chronic or active hepatitis B or C, requiring antiviral therapy Evidence of history of bleeding disorder, dialysis, or coexisting cancer that is distinct in primary site or histology from the cancer evaluated in this study Serious, uncontrolled infection Unresolved chronic toxicity > grade 1 from prior therapy Use of strong CYP3A4 inhibitors or strong inducers within 7 days prior to the start of study treatment and for the duration of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Biomarker-enriched advanced hematological neoplasms | Drug: BAY1251152<br>* Weekly infusion of BAY1251152 in 21-day cycles.<br>|
| Experimental: Arm 2<br>Other selected advanced hematological neoplasms | Drug: BAY1251152<br>* Weekly infusion of BAY1251152 in 21-day cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose(MTD) | To determine the MTD of BAY1251152 in subjects with advanced hematological neoplasms | 21 days | 
| Recommended Phase 2 dose (RP2D) | To determine the RP2D of BAY1251152 based on safety, tolerability, pharmacokinetic, and pharmacodynamic data in subjects with advanced hematological neoplasms | Up to 30 months | 
| Number of adverse events (AE) | For assessment of the safety (ECG, vital signs, clinical significant abnormal laboratory results… etc.)and tolerability of BAY 1251152 in subjects with advanced hematological neoplasms | Up to 30 months | 
| Pharmacokinetics (PK) is determined by maximum concentration (Cmax) |  | 21 days | 
| Pharmacokinetics (PK) is determined by Area Under concentration versus time Curve (AUC) |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response assessment of BAY 1251152 in hematological malignancies based on the internationally accepted criteria for the specific hematological malignancy which patient is suffering from | To assess the clinical efficacy of BAY 1251152 in subjects with advanced hematological neoplasms | Up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Dose escalation, Dose expansion, Positive transcription elongation factor b inhibitor, Cyclin-dependent kinase 9 inhibitor