COPANLISIB (BAY80-6946) Drug-drug Interaction and Cardiovascular Safety Study in Advanced Solid Tumor and Non-Hodgkin's Lymphoma Patients

Inclusion Criteria:

- Male or female patients ≥ 18 years of age with histological or cytological confirmed
advanced solid tumors or non-Hodgkin's lymphoma that have progressed on, or failed to
respond to, therapies known to provide clinical benefit may be enrolled after signing
informed consent.

- Normal left ventricular ejection fraction; adequate liver, renal and bone-marrow
functions as assessed by laboratory values.

- Adequate performance status and life expectancy of at least 3 months.

Exclusion Criteria:

- Solid-tumor patients with central nervous system (CNS) metastases if treatment
completed < 3 months before enrollment or lesions unstable or progressing on MRI scans
performed within 1 month of enrollment or unstable symptoms of the CNS metastases.

- Evidence of ventricular dysfunction such as congestive heart failure (CHF) or a
history of CHF greater than NYHA Class II

- Active coronary artery disease or myocardial infarction within the 6 months before
study entry; any new-onset angina within the 3 months before study entry or unstable
angina; cardiac arrhythmia requiring anti-arrhythmic therapy.

- Prior diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as fasting
blood or plasma glucose above 125 mg/dL under 2 separate days, corresponding to 6.94
mmol/L) or HbA1c ≥ 7%.

- Use of systemic including inhaled corticosteroids within the 2 days before the start
of study treatment (however, topical steroids are permitted).

- Known presence of human immunodeficiency virus (HIV) infection or active hepatitis (B
or C).

- Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic blood
pressure > 90 mmHg despite optimal medical management).

- Anticancer chemotherapy, hormone therapy or immunotherapy within the 4 weeks before
the first study treatment or scheduled for administration (of the above) during the
study

- History of, or concurrent, interstitial lung disease (ILD) or severely impaired
pulmonary function.

- Medications with drug-drug interaction potential for itraconazole which is to be
excluded before the study and during Cycle 1 such as CYP3A4 substrates with a narrow
therapeutic window or which have the potential to prolong QTc

- Concomitant medication contraindicated for use with rifampin (including, but not
limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide,
triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A
(HMG-CoA)-reductase inhibitors metabolised by CYP3A4, such as lovastatin and
simvastatin, ergot alkaloids metabolised by CYP3A4, such as dihydroergotamine,
ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine),
atazanavir, darunavir, fosamprenavir, ritonavir-boosted saquinavir, saquinavir, or
tipranavir