Copanlisib Given FDA Breakthrough Designation for Marginal Zone Lymphoma

Copanlisib has been granted with a breakthrough therapy designation from the FDA for the treatment of adult patients with relapsed marginal zone lymphoma who have received at least 2 prior therapies.

Scott Z. Fields, MD

Copanlisib (Aliqopa) has been granted with a breakthrough therapy designation from the FDA for the treatment of adult patients with relapsed marginal zone lymphoma (MZL) who have received at least 2 prior therapies.1

The designation, which will expedite the development and review of copanlisib in MZL, is based on data from the phase II CHRONOS-1 study, according to Bayer, the manufacturer of the PI3K inhibitor. In a subgroup of 23 patients with MZL, the overall response rate (ORR) was 69.6% (n = 16) in the primary analysis. A follow-up analysis at 18 months showed an ORR of 78.3% (n = 18) in these patients.

"The clinical evidence suggests that Aliqopa may address an unmet medical need by providing physicians and MZL patients with a therapy in a relapsed setting," Scott Z. Fields, MD, senior vice president and head of oncology development at Bayer's Pharmaceutical Division, said in a statement. "We will continue working closely with the FDA in order to bring Aliqopa to these underserved patients as soon as possible."

Safety data for the MZL subgroup showed that the most common (≥20%) all-grade treatment-emergent adverse events (TEAEs) were hyperglycemia and fatigue (47.8%), hypertension and diarrhea (43.5%), nausea (26.1%), and pyrexia and cough (21.7%). The most common grade 3 TEAEs were hypertension (39.1%) and hyperglycemia (34.8%).

Overall, the CHRONOS-1 study examined copanlisib in 142 patients across several lymphoma subtypes, including follicular lymphoma (grades 1-3a), MZL, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. Eligible patients had relapsed or refractory disease and failure of at least 2 prior lines of therapy.

Patients received copanlisib at 60 mg on days 1, 8, and 15, repeated every 28 days until disease progression or development of unacceptable toxicity. The primary endpoint was objective response by central review after a minimum of 16 weeks of treatment. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival, safety, and quality of life.

The median patient age was 63 years. The median time since the most recent disease progression was 8.3 months, and the study population had received a median of 3 prior regimens. All of the patients had prior exposure to rituximab (Rituxan) and 1 or more alkylating agents, and 60.6% had disease that was refractory to the last regimen received.

Across the lymphoma subgroups, 80.3% of the patients had advanced disease (stage III or IV) at enrollment. Follicular lymphoma was the dominant lymphoma subtype, accounting for 73.2% of the study population.

At the primary analysis, the ORR across all 142 patients was 59.2%, including complete responses in 12.0% of patients and partial responses in 47.2% of patients.2 The ORR rose to 60.6% in the full analysis set population analysis at 18 months. The median PFS was 11.2 months.

Based on the primary analysis, the FDA granted copanlisib an accelerated approval in September 2017 as a treatment for patients with relapsed follicular lymphoma who have received at least 2 least prior systemic therapies.

The accelerated approval is contingent on data from a confirmatory trial. Bayer has 2 ongoing phase III studies (CHRONOS-3 [NCT02367040] and CHRONOS-4 [NCT02626455]) exploring copanlisib in combination with other treatments in patients with relapsed indolent non-Hodgkin lymphoma.


  1. Bayer Receives U.S. FDA Breakthrough Therapy Designation for Aliqopa™ (copanlisib) for the Treatment of Marginal Zone Lymphoma. Published May 29, 2019. Accessed May 30, 2019.
  2. Dreyling M, Santoro A, Mollica L, et al. Copanlisib in patients with relapsed or refractory indolent B-cell lymphoma: primary results of the pivotal CHRONOS-1 study. Presented at: 2017 AACR Annual Meeting; April 1-5, 2017; San Washington, DC. Abstract CT149.