Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

An Open-label, Single-arm Phase II Study in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) to Evaluate Efficacy and Safety of Treatment With Single Agent Copanlisib and the Impact of Biomarkers Thereupon.

To assess the potential efficacy (in terms of objective response) of single agent copanlisib in patients with relapsed or refractory Diffuse large B-cell lymphoma (DLBCL) and assess the relationship between efficacy and a potentially predictive biomarker

Inclusion Criteria:

• Diagnosis of Diffuse large B-cell lymphoma (DLBCL) (de novo or DLBCL transformed from follicular lymphoma on the basis of a tissue biopsy).
• Received at least one prior therapy for aggressive Non-Hodgkin's Lymphoma (NHL) (DLBCL).
• Received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) + rituximab or equivalent regimen.
• Patients must have measurable disease.
• Not eligible or not willing to receive the high-dose (myeloablative) chemotherapy (HDC) and stem cell transplant (SCT).
• A fresh tumor biopsy collected during screening and /or archival tumor tissue collected after the last relapse/disease progression.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
• Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal (LLN) for the Institution. (as per local standard of care) as measured by echocardiogram (ECHO) or Multiple gated acquisition (MUGA) scan.
• Adequate bone marrow, liver and renal function.

Exclusion Criteria:

• Any of the following as the only site(s) of disease: palpable lymph nodes not visible on imaging studies, skin lesions, or bone marrow involvement only.
• Active CTCAE (Common Terminology Criteria for Adverse Events) Grade 3/4 infection.
• Current central nervous system (CNS) involvement by lymphoma.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction within the past 6 months before start of study treatment.
• Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).
• Type I or II diabetes mellitus with HbA1c > 8.5% at Screening.
• New York Heart Association (NYHA) class III or IV heart disease.
• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).
• Patients who previously received therapy with copanlisib or other PI3K inhibitors are not eligible for enrollment.