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

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