FDA Requests Withdrawal of Copanlisib in Relapsed Follicular Lymphoma

The FDA originally granted accelerated approval to copanlisib as a therapy for previously treated relapsed follicular lymphoma in September 2017 based on data from the phase 2 CHRONOS-1 study (NCT01660451).

Developers will work with the FDA to rescind a new drug application for copanlisib (Aliqopa) as a treatment for adult patients with relapsed follicular lymphoma previously treated with a minimum of 2 lines of systemic therapy, according to a press release from Bayer.¹

Patients who experienced a favorable response to treatment with copanlisib may be eligible to continue receiving the agent, including those for whom there are no appropriate alternative therapies. The press release advised that patients currently receiving copanlisib should talk with their health care providers, and that no new patients should initiate treatment with the agent.

The FDA originally granted accelerated approval to copanlisib as a therapy for previously treated relapsed follicular lymphoma in September 2017 based on data from the phase 2 CHRONOS-1 study (NCT01660451).² In a population of 104 patients with relapsed follicular B-cell non-Hodgkin lymphoma, investigators reported an overall response rate (ORR) of 59% (95% CI, 49%-68%). Additionally, copanlisib yielded a complete response (CR) rate of 14% and a median duration of response (DOR) of 12.2 months (range, 0+, 22.6).

Data from the CHRONOS-1 study highlighted serious adverse effects (SAEs) in 26% of the population. Common toxicities of this kind included pneumonia (8%), pneumonitis (5%), and hyperglycemia (5%).

The FDA requested additional data from the phase 3 CHRONOS-4 study (NCT02626455) to confirm the clinical benefits of copanlisib in this indication. Findings indicated that copanlisib plus immunochemotherapy did not fulfill the trial’s primary end point of progression-free survival (PFS) compared with immunochemotherapy alone. Investigators plan to disclose full results from the CHRONOS-4 study soon.

In part B of the CHRONOS-1 study, patients with relapsed/refractory follicular lymphoma received copanlisib infusions at a dose of 60 mg. The trial’s primary end point was ORR. Secondary end points included DOR, PFS, and overall survival (OS).

Patients 18 years and older with histologically confirmed indolent B-cell non-Hodgkin lymphoma that was relapsed or refractory following 2 or more prior lines of therapy were eligible for enrollment on the CHRONOS-1 study. Additional eligibility criteria included having an ECOG performance status of 0 to 2; adequate bone marrow, liver, and renal function; a life expectancy of 3 months or more; and availability of archival tumor tissue.

In the CHRONOS-4 study, patients received 60 mg infusions of copanlisib or matched placebo plus 375 mg/m2 of rituximab (Rituxan) every 4 weeks and 90 mg/m² of bendamustine on days 1 and 2 of each cycle, or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

The trial’s primary end point during the safety run-in portion was the recommended phase 3 dose of copanlisib when administered in combination with immunochemotherapy. Secondary end points included best overall response, ORR, DOR, CR rate, time to tumor progression, and OS.

Patients 18 years and older with grade 1, 2, or 3a follicular lymphoma; small lymphocytic lymphoma with adequate absolute lymphocyte counts; marginal zone lymphoma; or Waldenström macroglobulinemia were able to enroll on the CHRONOS-4 study. Additional inclusion criteria included having an ECOG performance status of no higher than 2 and adequate laboratory values within 7 days of study entry.

References

1. Bayer provides update on Aliqopa® (copanlisib). News release. Bayer. November 13, 2023. Accessed November 14, 2023. https://shorturl.at/kvzD3
2. Bayer receives FDA approval for Aliqopa™ (copanlisib) 60 mg vial for injection in adults with relapsed follicular lymphoma after two prior systemic therapies. News release. Bayer. September 14, 2017. Accessed November 14, 2023. https://shorturl.at/dAVYZ