Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

PRIMARY OBJECTIVES: I. To assess the safety, tolerability, and the maximum tolerated dose (MTD) of copanlisib hydrochloride (copanlisib) and venetoclax in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). (Phase 1) II. To estimate the efficacy (as measured by overall rate of response \[ORR\]) of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2) SECONDARY OBJECTIVES: I. To characterize the safety profile of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2) II. To evaluate duration of response (DOR) and progression-free survival (PFS) associated with combined administration of copanlisib/venetoclax. (Phase 2) III. To evaluate an overall survival (OS) associated with combined administration of copanlisib/venetoclax. (Phase 2) IV. To characterize the pharmacokinetics (PK) profile of copanlisib and venetoclax. (Phase 2) EXPLORATORY OBJECTIVES: I. Evaluate the emergence of resistant clones, as determined by the presence of novel mutations and expression of BCL2 family proteins. II. Characterize the T-cell population balance in patients treated with copanlisib/venetoclax. OUTLINE: This is a phase I, dose-escalation study of copanlisib hydrochloride, followed by a phase II study. Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15, and venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.