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

NCT03188965

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.

Related Conditions:
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Lung Adenocarcinoma
  • Malignant Solid Tumor
  • Non-Hodgkin Lymphoma
  • Ovarian Carcinoma
  • Prostate Carcinoma
  • Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • Neoplasms

Interventions

DrugSynonymsArms
BAY1895344Dose 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

NameTypeDescriptionInterventions
Dose escalation of BAY1895344 in Part AExperimentalSingle-agent dose-escalation part. Part A has the objective to define the MTD and / or RP2D.
  • BAY1895344
J-arm of Part AExperimentalSingle-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.
  • BAY1895344
Dose expansion of BAY1895344 in Part BExperimentalSingle-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.
  • BAY1895344

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 doseescalation 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 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 and loss of ATM protein by IHC,
             regardless of the cancer type.

        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:

               1. Hemoglobin ≥ 8.5 g/dL; patients with chronic erythropoietin treatment consistent
                  with institutional guidelines can be included.

               2. Absolute neutrophil count (ANC) ≥ 1.5X10* 9/L (≥ 1500/mm3)

               3. Platelet count ≥ 100X10*9/L (≥100,000/mm3)

        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:Up to 23 months or until discontinuation of study, whichever comes first
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:Up to 23 months or until discontinuation of study, whichever comes first
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:Up to 23 months or until discontinuation of study, whichever comes first
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

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