Copanlisib Chinese PK Study

Inclusion criteria

• Ability to understand and to sign an informed consent form. The informed consent must be signed before any study specific tests or procedures are done
• Chinese, age ≥ 18 years
• Patients with histologically confirmed indolent NHL (excluding chronic lymphocytic leukemia) that have relapsed and who are without past or current central nervous system involvement.
• Patients must have at least 1 measurable lesion according to the Lugano Classification.

• Patients affected by LPL/WM must have also measurable disease, defined as presence of IgM paraprotein with a minimum IgM level of equal to or greater than 2 times the upper limit of normal (ULN) OR over 10% of lymphoplasmacytic cells in bone marrow.
• Patients with splenic MZL with splenomegaly but no measurable lesion will be considered eligible.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) < 1.5 x the upper limit of normal (ULN)
• Adequate bone marrow, liver and renal function
• Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment
• Women of childbearing potential and men must agree to use highly effective contraception from signing of the informed consent form until at least 1 month after the last study drug administration. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control (failure rate of less than 1% per year), e.g. hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence

Exclusion criteria

Medical and surgical history:

• Uncontrolled hypertension (Blood pressure ≥ 150/90 mmHg despite optimal medical management)
• Proteinuria of CTCAE grade 3 or higher (> 3.5 g/24 h, measured by urine protein: creatinine ratio on a random urine sample)
• Known bleeding diathesis. Any hemorrhage or bleeding event ≥ Grade 3 within 28 days of start of study medication. (NCI-CTCAE Version 4.03)
• Uncontrolled diabetes with HbA1c ≥ 8.5%
• Ongoing cytomegalovirus (CMV) infection as confirmed by positive polymerase chain reaction (PCR) for CMV

Excluded previous therapies and medications:

• Prior treatment with PI3K inhibitors
• Anticancer chemotherapy or immunotherapy during the study or within 28 days of first study treatment.
• Patients must have recovered from the toxic effects (Grade <2) of the previous anti-cancer chemotherapy or immunotherapy (with the exception of alopecia)
• Biological response modifiers, such as Granulocyte colony stimulating factor (GCSF) within 14 days of first study treatment. G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the principal investigator; however they may not be substituted for a required dose reduction
• Use of strong inhibitors of CYP3A4 is prohibited from Day -14 and for the duration of the study
• Use of St John's Wort or strong inducers of CYP3A4 is prohibited from Day -14 and for the duration of the study