Phase IIa Study of Copanlisib in Relapsed or Refractory Mantle Cell Lymphoma (MCL)

A Single-arm, Open-label Phase IIa Study to Evaluate the Efficacy and Safety of Copanlisib Monotherapy in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL), Who Failed Ibrutinib Treatment or Were Unable to Tolerate Ibrutinib

The primary objective of this study is to assess objective response rate (ORR) in patients with relapsed or refractory MCL who failed ibrutinib treatment or were unable to tolerate ibrutinib.

Inclusion Criteria:

• Histologically confirmed MCL

• Patients who have previously received treatment with ibrutinib (modified by amendment 1), including:

  • Completion of at least 1 cycle of treatment with ibrutinib and confirmed evidence of disease progression or refractoriness to treatment or
  • Discontinuation of ibrutinib treatment at an earlier time due to toxicity

• Measurable disease according to the Lugano Classification

• At least 28 days or 5 half-lives, whichever is shorter, from the completion of anti-cancer treatment (including, but not limited to, immunotherapy, chemotherapy, targeted therapy and biologic therapy) to the start of study treatment, excluding ibrutinib where the window may be less and at minimum 3 days (modified by amendment 1)

• Availability of fresh tumor tissue at screening

• Male or female patients ≥ 18 years old

• ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2

• Left ventricular ejection fraction (LVEF) by echocardiogram or multiple gated acquisition (MUGA) scan ≥ the lower limit of normal (LLN) for the Institution

• 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
• Current central nervous system (CNS) involvement by lymphoma
• New York Heart Association (NYHA) class III or IV heart disease
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study treatment
• Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment) (modified by amendment 1)
• Type I or II diabetes mellitus with HbA1c > 8.5% at screening (modified by amendment 1)
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before start of study treatment. However, if a patient has recovered to ECOG performance status of ≤ 2 he/she may be enrolled provided that other eligibility criteria are met
• Ongoing or active infection of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3
• Known history of human immunodeficiency virus (HIV) infection
• Acute or chronic hepatitis B (HBV) or hepatitis C (HCV) infection requiring concomitant treatment prohibited by this protocol (i.e.immunosuppressive therapy)
• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
• Prior treatment with PI3K inhibitor(s)
• Cytomegalovirus (CMV) PCR positive at baseline